Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory enshea...Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.展开更多
Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenanc...Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.展开更多
Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the und...Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.展开更多
AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to s...AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)of<15 in the lower eyelid of each eye,and non-invasive tear break-up time(NI-TBUT)<10s,who were randomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with P<0.001.Multivariate analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,NIBUT,and OSDI.There was a significant difference between ILux®and MMGE(P<0.001)at follow-up from the first to the twelfth month in MGS,NI-BUT,and OSDI scores.No adverse events were reported.CONCLUSION:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.展开更多
BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were disco...BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.展开更多
Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigment...Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily cones.The mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of blindness.Understanding the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration process.Secondary cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a role.In this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor death.We also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial cells.The inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor degeneration.Furthermore,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.展开更多
The retina,as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new treatments.During the last decade is becoming clear that unilateral lesions in ...The retina,as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new treatments.During the last decade is becoming clear that unilateral lesions in bilateral areas of the central nervous system trigger an inflammatory response in the contralateral uninjured site.This effect has been better studied in the visual system where,as a rule,one retina is used as experimental and the other as control.Contralateral retinas in unilateral models of retinal injury show neuronal degeneration and glial activation.The mechanisms by which this adverse response in the central nervous system occurs are discussed in this review,focusing primarily on the visual system.展开更多
Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using re...Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.展开更多
AIM:To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients.METHODS:A retrospective study was performed on 19 dry eye patients(51.1...AIM:To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients.METHODS:A retrospective study was performed on 19 dry eye patients(51.1±16.0y).Non-invasive tear break-up time,tear meniscus height,meibomian gland loss,lipid layer thickness,conjunctival redness,corneal staining,ocular surface disease index(OSDI),and ocular pain intensity were measured before(baseline),1wk,and 2mo after lid scrubbing with a gel containing different natural extracts(okra extract,aloe vera leaf juice,hydrolysed soy protein,caffeine,citrus unshiu peel extract,and raspberry seed oil).RESULTS:Compared with the baseline,there was a statistically significant improvement in both first(P=0.048)and average(P=0.026)non-invasive tear break-up time 2mo after treatment,as well as in corneal staining(P=0.043,0.012),OSDI(P<0.001),and ocular pain intensity(P<0.001)after 1wk and 2mo.In addition,there was no correlation between ocular signs and symptoms.CONCLUSION:The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability,corneal damage,and ocular symptoms,which is the reason why this therapeutic procedure is proposed as an alternative for dry eye management.However,it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel,primarily due to the absence of a negative control group.展开更多
Glaucoma is a neurodegenerative chronic pathology,characterized by the loss of retinal ganglion cells(RGC),which leads to an irreversible vision field loss.The increased intraocular pressure(IOP)constitutes its main r...Glaucoma is a neurodegenerative chronic pathology,characterized by the loss of retinal ganglion cells(RGC),which leads to an irreversible vision field loss.The increased intraocular pressure(IOP)constitutes its main risk factor.Nowadays,the main treatments for glaucoma are focused on decreasing IOP;nevertheless,the progression of the disease continues,despite IOP control.This fact shows the existence of other factors that could contribute to the advance of glaucomatous neurodegeneration.The early diagnostics,the use of neuroprotective therapies,and knowledge of the pathological processes are the major challenges associated with the management of this disease.Different pathogenic mechanisms have been proposed to be responsible for RGC death,including oxidative stress,mitochondrial dysfunction,glutamate excitotoxicity,and neuroinflammation(Casson et al.,2012).展开更多
AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical record...AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical records was carried out, identifying cases of globe penetration secondary to peribulbar anesthesia injection during 5 y activity in Centro de Oftalmología Barraquer. RESULTS: A total of 17 460 needle-based ocular anesthesia procedures were performed in our centre and 4 cases of globe penetration were recorded with an estimated prevalence of 0.024%. Globe penetrations were always detected in the first 24 h after surgery. Vitreous haemorrhage was found in all the cases. Two eyes presented retinal detachment and two eyes choroidal detachment(CD). The initial surgical approach was performed within the first 48 h. Silicone oil was used as tamponade in three eyes and the fourth case remained only with air. Detachments were solved successfully in all the cases. Functional results varied among cases, depending on ocular remarkable antecedent and globe penetration with or without retinal or CD.CONCLUSION: Prevalence of globe penetration during loco-regional anesthesia is low in our centre. Physicians should consider the possibility of globe penetration in eyes with postoperative atypical appearance after locoregional anesthesia. Immediate B-scan ultrasonography is recommended in suspicious cases with a dense vitreous haemorrhage. An early vitrectomy surgery in conjunction with laser or cryotherapy at the penetration sites is essential for good anatomical and functional results.展开更多
Background:Dry eye is a multifactor disease of the tear film and ocular surface that substantially affects quality of life.Case presentation:Dobesilate administered as eye drops was well tolerated and effective in tre...Background:Dry eye is a multifactor disease of the tear film and ocular surface that substantially affects quality of life.Case presentation:Dobesilate administered as eye drops was well tolerated and effective in treating both the objective signs and subjective symptoms of dry eye disease in this 2-week study.Conclusion:To the best of our knowledge,this is the first clinical report of using dobesilate in eye drops.Dobesilate may provide a novel approach to treating drying diseases of the eye.展开更多
Retinal ganglion cells（RGCs）are located in the innermost layer of the retina and are the only retinal output neurons,conveying light information to the main retinorecipient target regions of the brain responsible fo...Retinal ganglion cells（RGCs）are located in the innermost layer of the retina and are the only retinal output neurons,conveying light information to the main retinorecipient target regions of the brain responsible for the image-and non-image-forming visual functions.There are well over twenty RGC types,each with its own dendritic morphology and physiological characteristics,展开更多
Taurine(2-amino-ethanesulfonic acid)is a naturally occurring amino sulfonic acid derived from cysteine and methionine metabolism.Its common name derives from the ox,as it was first isolated from the bile of an ox(Frog...Taurine(2-amino-ethanesulfonic acid)is a naturally occurring amino sulfonic acid derived from cysteine and methionine metabolism.Its common name derives from the ox,as it was first isolated from the bile of an ox(Froger et al.,2014).The molecular structure of taurine differs from that of amino acids by the presence of a sulfonic acid,instead of the more common carboxylic acid group in the structure of amino acids.展开更多
Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2...Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.展开更多
Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in t...Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the world.At present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal cells.Thus,these diseases are nowadays one of the greatest challenges in the field of ophthalmological research.Bone marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor degenerations.These cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor degenerations.Furthermore,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent cells.The intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect photoreceptors.Therefore,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.展开更多
The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has t...The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.展开更多
AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classific...AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.展开更多
Dear Editor,I am Dr.Santiago Montolío-Marzo from FISABIO Oftalmología Médica,Valencia,Spain.I write you to present a case report of epithelial downgrowth in an aphakic patient.Intracameral epithelial do...Dear Editor,I am Dr.Santiago Montolío-Marzo from FISABIO Oftalmología Médica,Valencia,Spain.I write you to present a case report of epithelial downgrowth in an aphakic patient.Intracameral epithelial downgrowth is one of the most feared complications in cases of penetrating ocular trauma or recurrent ocular surgeries.Its progress can affect all the ocular structures,giving rise to corneal decompensation,retinal detachment,difficult-to-treat glaucoma or phthisis bulbi and many cases end in enucleation[1].Fortunately,the incidence of this condition is very low,there being between 0.08%and 0.12%after cataract surgery and 0.25%after penetrating keratoplasty.Its infrequency means that scientific evidence is reduced to case series and the opinions of experts without there being a homogeneous criterion to guide the work of the doctor in charge.For these reasons,epithelial downgrowth is still a diagnostic and therapeutic challenge.展开更多
Techniques to label the neuroretina and the retinal pigment epithelium(RPE)have been the topic of many studies for years.The reliability and reproducibility of these techniques are essential to investigate retinal alt...Techniques to label the neuroretina and the retinal pigment epithelium(RPE)have been the topic of many studies for years.The reliability and reproducibility of these techniques are essential to investigate retinal alterations of ocular pathologies and possible treatments.In particular,the study of the integrity of the RPE is of great importance in pathologies such as retinitis pigmentosa or age-related macular degeneration(Gu et al.,2012;Fisher and Ferrington,2018;Zhang et al.,2019).The most common approaches use antibodies to identify different cell populations.Recently,we have described a novel technique to study the integrity of the neuroretina and the RPE,as well as the functionality of the RPE in rats(Valiente-Soriano et al.,2020).展开更多
基金supported by the Spanish Ministry of Economy and Competitiveness,No.PID2019-106498GB-I00(to MVS)the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”,No.PI19/00071(to MAB)+1 种基金Ministerio de Ciencia e Innovación Project,No.SAF2017-82736-C2-1-R(to MTMF)in Universidad Autónoma de MadridFundación Universidad Francisco de Vitoria(to JS)。
文摘Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.
基金supported by Instituto de Salud CarlosⅢ(ISCⅢ):PI19/00203cofunded by ERDF+9 种基金"A way to make Europe"to MPVP and DGAP122/00900RD16/0008/0026 co-funded by ERDF"A way to make Europe"to MPVP and RD21/0002/0014financiado porla Unión Europea-NextGenerationEUFundación Robles Chillida to DGARED2018-102499-TPID201 9-106498GB-I00funded by MCIN/AEI/10.13039/501100011 033 to MVSIHU FOReSIGHT[ANR-18-IAHU-0001] to SP
文摘Taurine is considered a non-essential amino acid because it is synthesized by most mammals.However,dietary intake of taurine may be necessary to achieve the physiological levels required for the development,maintenance,and function of certain tissues.Taurine may be especially important for the retina.The concentration of taurine in the retina is higher than that in any other tissue in the body and taurine deficiency causes retinal oxidative stress,apoptosis,and degeneration of photoreceptors and retinal ganglion cells.Low plasma taurine levels may also underlie retinal degeneration in humans and therefore,taurine administration could exert retinal neuroprotective effects.Taurine has antioxidant,anti-apoptotic,immunomodulatory,and calcium homeostasis-regulatory properties.This review summarizes the role of taurine in retinal health and disease,where it appears that taurine may be a promising nutraceutical.
基金funded by the Spanish Ministry of Economy and Competitiveness,No.PID(2019)-106498GB-100 (to MVS)by the Instituto de Salud CarlosⅢ,Fondo Europeo de Desarrollo Regional"Una manera de hacer Europa",No.PI19/00071 (to MAB)+2 种基金the RETICS subprograms of Spanish Networks OftoRed,Nos.RD16/0008/0026 (to DGB) and RD16/0008/0016 (to DGB)RICORS Terav,No.RD16/0011/0001 (to DGB)from Instituto de Salud CarlosⅢby the Fundacion Seneca,Agencia de Cienciay Tecnologia Región de Murcia,No.19881/GERM/15 (all to MVS)
文摘Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.
文摘AIM:To compare the safety and effectiveness of eyelid treatment with the ILux®-MGD Treatment System in one session versus five sessions of mechanical meibomian gland expression(MMGE)in patients with moderate to severe meibomian gland dysfunction(MGD).METHODS:A prospective,randomized,open-label,and controlled clinical trial that compared one session of the ILux®MGD Treatment System versus five sessions of MMGE in both eyes of 130 patients aged≥18y with Ocular Surface Disease Index(OSDI)scores≥13,total meibomian gland scores(MGS)of<15 in the lower eyelid of each eye,and non-invasive tear break-up time(NI-TBUT)<10s,who were randomized 1:1 to ILux®or MMGE.RESULTS:The mean age was 58±17.49y.Baseline total MGS scores in both treatment groups were comparable.During follow-up,there were significant differences in total MGS and per sector with P<0.001.Multivariate analysis was performed using generalized estimating equations corresponding to the generalized linear model for repeated means to determine the treatment relationship with total MGS,NIBUT,and OSDI.There was a significant difference between ILux®and MMGE(P<0.001)at follow-up from the first to the twelfth month in MGS,NI-BUT,and OSDI scores.No adverse events were reported.CONCLUSION:ILux®treatment compared to MMGE significantly improves symptoms and signs in patients with moderate to severe MGD for one year without adverse events.
文摘BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.
基金supported by grants from Fundación Séneca,Agencia de Cienciay Tecnología Región de Murcia,No.19881/GERM/15(to MVS)Spanish Ministry of Economy and Competitiveness,Instituto de Salud Carlos Ⅲ,Fondo Europeo de Desarrollo Regional ‘‘Una 30 Manera de Hacer Europa’’,No.SAF2015-67643-P(to MVS),PI16/00380(to MPVP),RD16/0008/0026(to MPVP),PI16/00031(to MAB)
文摘Inherited photoreceptor degeneration in humans constitutes a major cause of irreversible blindness in the world.They comprise various diseases,but retinitis pigmentosa is the most frequently observed.Retinitis pigmentosa is commonly limited to the eye,where there is progressive photoreceptor degeneration,rods and secondarily cones.The mechanisms of cone and rod degeneration continue to be investigated,since most of the mutations causing retinitis pigmentosa affect rods and thus,the secondary death of cones is an intriguing question but,ultimately,the cause of blindness.Understanding the mechanisms of rod and cone degeneration could help us to develop therapies to stop or,at least,slow down the degeneration process.Secondary cone degeneration has been attributed to the trophic dependence between rods and cones,but microglial cell activation could also have a role.In this review,based on previous work carried out in our laboratory in early stages of photoreceptor degeneration in two animal models of retinitis pigmentosa,we show that microglial cell activation is observed prior to the the initiation of photoreceptor death.We also show that there is an increase of the retinal microglial cell densities and invasion of the outer retinal layers by microglial cells.The inhibition of the microglial cells improves photoreceptor survival and morphology,documenting a role for microglial cells in photoreceptor degeneration.Furthermore,these results indicate that the modulation of microglial cell reactivity can be used to prevent or diminish photoreceptor death in inherited photoreceptor degenerations.
基金supported by the Spanish Ministry of Economy and Competitiveness,Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071[to MAB],PID2019-106498GB-I00[to MVS],RD16/0008/0026[to MVS]and RD16/0008/0016[to MVS])the Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)(to MVS).
文摘The retina,as part of the central nervous system is an ideal model to study the response of neurons to injury and disease and to test new treatments.During the last decade is becoming clear that unilateral lesions in bilateral areas of the central nervous system trigger an inflammatory response in the contralateral uninjured site.This effect has been better studied in the visual system where,as a rule,one retina is used as experimental and the other as control.Contralateral retinas in unilateral models of retinal injury show neuronal degeneration and glial activation.The mechanisms by which this adverse response in the central nervous system occurs are discussed in this review,focusing primarily on the visual system.
基金supported by the Spanish Ministry of Economy and Competitiveness(PID2019-106498GB-I0)Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071)+2 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)Spanish Ministry of Science and Innovation(PID 2019-106498 GB-I00)Intramural Research Program of the National Eye Institute,National Institutes of Health(NIH/NEI RO1 EY029087)。
文摘Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.
文摘AIM:To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients.METHODS:A retrospective study was performed on 19 dry eye patients(51.1±16.0y).Non-invasive tear break-up time,tear meniscus height,meibomian gland loss,lipid layer thickness,conjunctival redness,corneal staining,ocular surface disease index(OSDI),and ocular pain intensity were measured before(baseline),1wk,and 2mo after lid scrubbing with a gel containing different natural extracts(okra extract,aloe vera leaf juice,hydrolysed soy protein,caffeine,citrus unshiu peel extract,and raspberry seed oil).RESULTS:Compared with the baseline,there was a statistically significant improvement in both first(P=0.048)and average(P=0.026)non-invasive tear break-up time 2mo after treatment,as well as in corneal staining(P=0.043,0.012),OSDI(P<0.001),and ocular pain intensity(P<0.001)after 1wk and 2mo.In addition,there was no correlation between ocular signs and symptoms.CONCLUSION:The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability,corneal damage,and ocular symptoms,which is the reason why this therapeutic procedure is proposed as an alternative for dry eye management.However,it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel,primarily due to the absence of a negative control group.
基金supported by the Ophthalmological Network OFTARED(RD16/0008/0005),of the Institute of Health of CarlosⅢof the Spanish Ministry of Economy(to AIR,RDH,and JJS)Santander-Complutense University of Madrid Research Projects(PR75/18-21560)(to AIR,RNH,and JJS)supported by a Predoctoral Fellowship(FPU17/01023)from the Spanish Ministry of Science,Innovation,and Universities。
文摘Glaucoma is a neurodegenerative chronic pathology,characterized by the loss of retinal ganglion cells(RGC),which leads to an irreversible vision field loss.The increased intraocular pressure(IOP)constitutes its main risk factor.Nowadays,the main treatments for glaucoma are focused on decreasing IOP;nevertheless,the progression of the disease continues,despite IOP control.This fact shows the existence of other factors that could contribute to the advance of glaucomatous neurodegeneration.The early diagnostics,the use of neuroprotective therapies,and knowledge of the pathological processes are the major challenges associated with the management of this disease.Different pathogenic mechanisms have been proposed to be responsible for RGC death,including oxidative stress,mitochondrial dysfunction,glutamate excitotoxicity,and neuroinflammation(Casson et al.,2012).
文摘AIM: To describe prevalence and different clinical signs and management of cases with penetrating eye injuries during loco-regional anesthesia for ophthalmic surgery. METHODS: A retrospective review of clinical records was carried out, identifying cases of globe penetration secondary to peribulbar anesthesia injection during 5 y activity in Centro de Oftalmología Barraquer. RESULTS: A total of 17 460 needle-based ocular anesthesia procedures were performed in our centre and 4 cases of globe penetration were recorded with an estimated prevalence of 0.024%. Globe penetrations were always detected in the first 24 h after surgery. Vitreous haemorrhage was found in all the cases. Two eyes presented retinal detachment and two eyes choroidal detachment(CD). The initial surgical approach was performed within the first 48 h. Silicone oil was used as tamponade in three eyes and the fourth case remained only with air. Detachments were solved successfully in all the cases. Functional results varied among cases, depending on ocular remarkable antecedent and globe penetration with or without retinal or CD.CONCLUSION: Prevalence of globe penetration during loco-regional anesthesia is low in our centre. Physicians should consider the possibility of globe penetration in eyes with postoperative atypical appearance after locoregional anesthesia. Immediate B-scan ultrasonography is recommended in suspicious cases with a dense vitreous haemorrhage. An early vitrectomy surgery in conjunction with laser or cryotherapy at the penetration sites is essential for good anatomical and functional results.
文摘Background:Dry eye is a multifactor disease of the tear film and ocular surface that substantially affects quality of life.Case presentation:Dobesilate administered as eye drops was well tolerated and effective in treating both the objective signs and subjective symptoms of dry eye disease in this 2-week study.Conclusion:To the best of our knowledge,this is the first clinical report of using dobesilate in eye drops.Dobesilate may provide a novel approach to treating drying diseases of the eye.
基金supported by Spanish Ministry of Economy and Competitiveness:SAF-2012-38328ISCIII-FEDER"Una manera de hacer Europa"PI13/01266,PI13/00643,RETICS:RD12/0034/0014
文摘Retinal ganglion cells（RGCs）are located in the innermost layer of the retina and are the only retinal output neurons,conveying light information to the main retinorecipient target regions of the brain responsible for the image-and non-image-forming visual functions.There are well over twenty RGC types,each with its own dendritic morphology and physiological characteristics,
基金supported by Instituto de Salud CarlosⅢ(ISCⅢ):PI19/00203,co-funded by ERDF“A way to make Europe”to MPVP and DGA,RD16/0008/0026 co-funded by ERDF+3 种基金“A way to make Europe”to MPVP and RD21/0002/0014 financiado por la Unión Europea–Next Generation EUFundación Robles Chillida to DGAthe RHU LIGHT4DEAF[ANR-15-RHU-0001]IHU FORe SIGHT[ANR-18-IAHU-0001]to SP。
文摘Taurine(2-amino-ethanesulfonic acid)is a naturally occurring amino sulfonic acid derived from cysteine and methionine metabolism.Its common name derives from the ox,as it was first isolated from the bile of an ox(Froger et al.,2014).The molecular structure of taurine differs from that of amino acids by the presence of a sulfonic acid,instead of the more common carboxylic acid group in the structure of amino acids.
文摘Vitreous hemorrhages are important clinical manifestations of proliferative diabetic retinopathy. Non-cleared vitreous hemorrhages could lead to hemosiderosis bulbi and glaucoma. Here, we describe the case of a type 2 diabetic patient presenting anterior segment and vitreous hemorrhages that resolved three days after treatment with a single intravitreal injection of dobesilate.
基金by Fundación Lucha contra la Ceguera(FUNDALUCE)to MPVPFundación Robles Chillida to DGA+1 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15 to MVS)the Spanish Ministry of Science and Innovation,Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una Manera de Hacer Europa”(SAF2015-67643-P to MVS,PI19/00203 to MPVP and DGA,RD16/0008/0026 to MPVP,RED2018-102499-T to MVS).
文摘Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the world.At present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal cells.Thus,these diseases are nowadays one of the greatest challenges in the field of ophthalmological research.Bone marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor degenerations.These cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor degenerations.Furthermore,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent cells.The intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect photoreceptors.Therefore,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.
基金This work was supported by grants from the Spanish Ministerio de Ciencia y Tecnología(BFU2007-67540)Ministerio de Economía y Competitividad(CGL2015-64650P)+1 种基金Dirección General de Investigación del Ministerio de Educación y Ciencia(BFU2017-85547-P)Junta de Extremadura,Fondo Europeo de Desarrollo Regional,“Una manera de hacer Europa”(GR15158,GR18114,IB18113).
文摘The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in humans.Throughout vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller glia.The proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very low.This region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal neurons.Therefore,regenerative response after injury occurs with low efficiency in the precocial avian retina.In contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at hatching.In particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear layer.Therefore,stem cell niches are very active in the retina of altricial birds.Although more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.
文摘AIM:To provide an epidemiological characterization of ocular cicatricial pemphigoid(OCP)in Colombia.METHODS:We conducted a cross-sectional study using SISPRO.We applied the specific code of the International Classification of Diseases for Ocular Pemphigoid,from 2009-2019 to estimate prevalence,incidence,and the demographic status of the disease in Colombia.RESULTS:The estimated average prevalence was 0.22 per 1000000 inhabitants,and the estimated average incidence was 0.24 per 1000000 inhabitants.With a female predominance of 62.5%,and a male/female ratio of 1:1.6.The group of patients diagnosed with the disease after the age of 80 presented the highest prevalence.The departments with the highest prevalence were Antioquia,Bogotá,and Santander.CONCLUSION:There are important differences between worldwide and Colombian prevalence and incidence data,which may be related to genetic and epigenetic factors,and the possible underdiagnosis of the disease.According to the results,OCP is an extremely rare disease in Colombia.Nevertheless,it is important to encourage awareness of the disease due to its devastating consequences.
文摘Dear Editor,I am Dr.Santiago Montolío-Marzo from FISABIO Oftalmología Médica,Valencia,Spain.I write you to present a case report of epithelial downgrowth in an aphakic patient.Intracameral epithelial downgrowth is one of the most feared complications in cases of penetrating ocular trauma or recurrent ocular surgeries.Its progress can affect all the ocular structures,giving rise to corneal decompensation,retinal detachment,difficult-to-treat glaucoma or phthisis bulbi and many cases end in enucleation[1].Fortunately,the incidence of this condition is very low,there being between 0.08%and 0.12%after cataract surgery and 0.25%after penetrating keratoplasty.Its infrequency means that scientific evidence is reduced to case series and the opinions of experts without there being a homogeneous criterion to guide the work of the doctor in charge.For these reasons,epithelial downgrowth is still a diagnostic and therapeutic challenge.
基金This work was supported by the Spanish Ministry of Economy and Competitiveness,Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071 to MAB,PID2019-106498GB-I00,RD16/0008/0026 and RD16/0008/0016 to MVS)by the Fundación Seneca,Agencia de Ciencia y Tecnologia Region de Murcia(19881/GERM/15,to MVS).
文摘Techniques to label the neuroretina and the retinal pigment epithelium(RPE)have been the topic of many studies for years.The reliability and reproducibility of these techniques are essential to investigate retinal alterations of ocular pathologies and possible treatments.In particular,the study of the integrity of the RPE is of great importance in pathologies such as retinitis pigmentosa or age-related macular degeneration(Gu et al.,2012;Fisher and Ferrington,2018;Zhang et al.,2019).The most common approaches use antibodies to identify different cell populations.Recently,we have described a novel technique to study the integrity of the neuroretina and the RPE,as well as the functionality of the RPE in rats(Valiente-Soriano et al.,2020).
