Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs worldwide.Due to the aging population,it is expected that the number of peopl...Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs worldwide.Due to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more prevalent.Glaucoma primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.展开更多
AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact lenses.M...AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact lenses.METHODS:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye preparation.UV light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye structure.In the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the vitreous.Subsequently,UVprotective contact lenses were placed over the structures,and UV light penetrance was measured.Measurements of UV light exposure were taken outdoors at various locations and times.RESULTS:Cornea absorbed 63.56%of UV light that reached the eye.Cornea and lens absorbed 99.34%of UV light.Whole eye absorbed 99.77%of UV light.When UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,respectively.UV light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a beach.CONCLUSION:Cornea absorbs the majority of UV light that reaches the eye in this model.UV-protective contact lenses reduce UV exposure to the eye.Locations with high albedo expose the eye to higher levels of UV light.展开更多
AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths(ALs) at one United States Veterans Affairs teaching hospital.METHODS: A retrospective chart review was conducted f...AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths(ALs) at one United States Veterans Affairs teaching hospital.METHODS: A retrospective chart review was conducted from November 2013 to May 2018. One eye of each patient who underwent cataract surgery with a monofocal intraocular lens(IOL) was included. The range of postoperative follow-up period was from 3 wk to 4 mo. The Holladay 2, Barrett Universal II, and Hill-Radial Basis Function(Hill-RBF) formulae were used to predict the postoperative refraction for all cataract surgeries. For each formula, we calculated the prediction errors [including mean absolute prediction error(MAE)] and the percentage of eyes within ±0.25 diopter(D) and ±0.5 D of predicted refraction. We performed subgroup analyses for short(AL<22.0 mm), medium(AL 22.0-25.0 mm), and long eyes(AL>25.0 mm).RESULTS: A total of 1131 patients were screened, and 909 met the inclusion criteria. Resident ophthalmologists were the primary surgeons in 710(78.1%) cases. We found no statistically significant difference in predictive accuracy among the three formulae over the entire AL range or in the short, medium, and long eye subgroups. Across the entire AL range, the Hill-RBF formula resulted in the lowest MAE(0.384 D) and the highest percentage of eyes with postoperative refraction within ±0.25 D(42.7%) and ±0.5 D(75.5%) of predicted. All three formulae had the highest MAEs(>0.5 D) and lowest percentage within ±0.5 D of predicted refraction(<55%) in short eyes.CONCLUSION: In cataract surgery patients at our teaching hospital, three commonly used biometric formulae demonstrate similar refractive accuracy across all ALs. Short eyes pose the greatest challenge to predicting postoperative refractive error.展开更多
Oxidative stress and cyclic adenosine 3′,5′-monophosphate(cAMP)/protein kinase A(PKA)pathway in the optic nerve head astrocytes:Glaucoma is a leading cause of blindness worldwide in individuals 60 years of age and o...Oxidative stress and cyclic adenosine 3′,5′-monophosphate(cAMP)/protein kinase A(PKA)pathway in the optic nerve head astrocytes:Glaucoma is a leading cause of blindness worldwide in individuals 60 years of age and older.Despite the widely appreciated disease relevance of structural and functional abnormalities of astrocyte in the optic nerve head(ONH)that is associated with retinal ganglion cell(RGC)axon degeneration,the molecular mechanisms underlying astrocyte dysfunction in glaucomatous ONH degeneration are poorly understood.Oxidative stress is strongly linked to glaucoma pathogenesis,and astrocytes are the responsible cell type that is mostly related to oxidative stress and glaucomatous ONH degeneration.展开更多
Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD includes soft drusen and pigmentary changes in the retinal pigment epithelium (RPE). ...Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD includes soft drusen and pigmentary changes in the retinal pigment epithelium (RPE). As people age, such soft confluent drusen can progress into two forms of advanced AMD, geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD) and result in the loss of central vision. The exact mechanism for developing early AMD and progressing to advanced stage of disease is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as the cause of AMD progression. Together, complement factor H (CFH) and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress from activities such as smoking has also demonstrated a powerful contribution to AMD progression. To extend our previous finding that genetic polymorphisms in CFH results in OxPLs and the risk-form of CFH (CFH Y402H) has reduced affinity for oxidized phospholipids, and subsequent diminished capacity which subsequently diminishes the capability to attenuate the inflammatory effects of these molecules, we compared the binding properties of CFH and CFH related protein 1 (CFHR1), which is also associated with disease risk, to OxPLs and their effects on modulating inflammation and lipids uptake. As both CFH-402H and CFHR1 are associated with increased risk to AMD, we hypothesized that like CFH-402H, CFHR1 contribution to AMD risk may also be due to its diminished affinity for OxPLs. Interestingly, we found that association of CFHR1 with OxPLs was not statistically different than CFH. However, binding of CFHR1 did not elicit the same protective benefits as CFH in that both inflammation and lipid uptake are unaffected by CFHR1 association with OxPLs. These findings demonstrate a novel and interesting complexity to the potential interplay between the complement system and oxidative stress byproducts, such as OxPLs, in the mechanistic contribution to AMD. Future work will aim to identify the molecular distinctions between CFH and CFHR1 which confer protection by the former, but not latter molecules. Understanding the molecular domains necessary for protection could provide interventional insights in the generation of novel therapeutics for AMD and other diseases associated with oxidative stress.展开更多
AIM:To evaluate the safety and efficacy of posterior scleral application(a modified technique)of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.METHODS:This retrospective stud...AIM:To evaluate the safety and efficacy of posterior scleral application(a modified technique)of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.METHODS:This retrospective study included 101 patients(115 eyes)with glaucoma(aged 12–83y)who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method.A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus.The mitomycin C concentration and exposure time were 0.2–0.5 mg/m L and 1–5min,respectively.Intraocular pressure,bestcorrected visual acuity,and hypotensive medications were recorded at baseline and at the final visit.Complications,interventions required,and bleb morphology were recorded postoperatively.The primary outcome was trabeculectomy safety,including complications and bleb morphology;the secondary outcome was the trabeculectomy success rate.RESULTS:At the final follow-up[median 28mo,range 7–67mo and interquartile range(IQR)13mo],the qualified(cumulative)success rate was 93.0%and the complete success rate was 60.0%.No bleb-related complications were observed.The mean height,extent,and vascularity grades were 0.6±0.9,1.1±0.4,and 2.4±0.9,respectively.All Seidel tests were negative.The mean posteriority grade was 0.8±0.4.CONCLUSION:Trabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.展开更多
Diabetic retinopathy(DR)is the most common microvascular complication in patients with diabetes mellitus(DM),and remains the single greatest cause of blindness in working age adults around the world.In this article,we...Diabetic retinopathy(DR)is the most common microvascular complication in patients with diabetes mellitus(DM),and remains the single greatest cause of blindness in working age adults around the world.In this article,we review the evolution of pharmacotherapies for both diabetic macular edema(DME)and DR such as anti-vascular endothelial growth factor inhibitors and various steroid formulations,as well as other emerging pharmacotherapies currently in late stage clinical testing for this disease.展开更多
The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental(OFCD)syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient...The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental(OFCD)syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296 delT in exon4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.展开更多
The human lens is composed anteriorly of a single layer of epithelial cells, which undergo mitosis and migrate to the lens equator where they differentiate into lens fiber cells [1]. The elongated lens fiber cells exp...The human lens is composed anteriorly of a single layer of epithelial cells, which undergo mitosis and migrate to the lens equator where they differentiate into lens fiber cells [1]. The elongated lens fiber cells express high levels of soluble crystallin proteins that do not undergo turnover and must remain relatively stable over a lifetime. The three- dimensional organization of crystallins is crucial for lens transparency and refractive power and therefore visual acu- ity.展开更多
Since the concept of signal transduction was introduced in the 1970s,various signal transduction pathways and signaling molecules have been identified.A major driving force in this field is the potential for signaling...Since the concept of signal transduction was introduced in the 1970s,various signal transduction pathways and signaling molecules have been identified.A major driving force in this field is the potential for signaling pathway-targeted therapy in clinical applications.展开更多
Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without...Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.展开更多
Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema,which is the leading hypothesis of acute mountai...Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema,which is the leading hypothesis of acute mountain sickness(AMS).However,studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature.This study aimed to investigate ocular microcirculation alterations,the only visualized capillaries in the central neural system(CNS),during early-stage AMS using a hypobaric chamber.This study found that after high altitude simulation,the optic nerve showed retinal nerve fiber layer thickening(P=0.004–0.018)in some locations,and the area of the optic nerve subarachnoid space(P=0.004)enlarged.Optical coherence tomography angiography(OCTA)showed increased retinal radial peripapillary capillary(RPC)flow density(P=0.003–0.046),particularly on the nasal side of the nerve.The AMSpositive group had the largest increases in RPC flow density in the nasal sector(AMS-positive,?3.21±2.37;AMS-negative,?0.01±2.16,P=0.004).Among multiple ocular changes,OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms(beta=0.222,95%CI,0.009–0.435,P=0.042).The area under the receiver operating characteristics curve(AUC)for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882(95%CI,0.746–0.998).The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS.RPC OCTA endpoints may serve as a rapid,noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes.展开更多
Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been...Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.展开更多
Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced...Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD.We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status.Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages.The algorithm could also be potentially applied for therapeutic response,and toward personalized care and precision medicine.展开更多
Advanced sustainable biomedical materials are urgently needed for clinical applications;however,developing biomedical materials with exceptional mechanical and bactericidal properties as well as removable functionalit...Advanced sustainable biomedical materials are urgently needed for clinical applications;however,developing biomedical materials with exceptional mechanical and bactericidal properties as well as removable functionalities to reduce unintended secondary injury remains a challenge.Here,we report a biomass-derived composite consisting of water-soluble fish gelatin(FG)and antibacterial ZnO@silk fibroin(ZSF)microspheres for potential application as the wound dressing.The ZSF microspheres are embedded in a FG matrix to realize the stretchable,antibacterial,and removable ZSF/FG composites.By introducing glycerin as the plasticizer,ZSF/FG composites deliver a tensile strength of 4.5 MPa and stretchability of 550%.Acting as both the germicide and hydrophile components,ZSF microspheres endow the composites with excellent antibacterial capacity and water solubility.To prevent secondary injury,the ZSF/FG composites can be easily removed from the wounds by simply exposing them to excess water.Additionally,the ZSF/FG composites exhibit favorable biocompatibility and sustain high cell viability of over 100%.The full-thickness skin wound model on infected mice demonstrated an efficient rate of wound closure and a reduced inflammatory response.The ZSF/FG composite shows promise to hasten the healing of infected wounds and is expected a promising candidate as wound dressing for clinical therapy.展开更多
Retinal degenerative diseases are a major cause of blindness.Retinal gene therapy is a trail-blazer in the human gene therapy field,leading to the frst FDA approved gene therapy product for a human genetic disease.The...Retinal degenerative diseases are a major cause of blindness.Retinal gene therapy is a trail-blazer in the human gene therapy field,leading to the frst FDA approved gene therapy product for a human genetic disease.The application of Clustered Regularly Interspaced Short Palindromic Repeat/Cas9(CRISPR/Cas9)-mediated gene editing technology is transforming the delivery of gene therapy.We review the history,present,and future pro-spects of retinal gene therapy.展开更多
The Future Forum,a non-profit organization established last year in Beijing,announced that pathologist Dennis Ming Yuk Lo from the Chinese University of Hong Kong won the life sciences Future Science Prize for the dis...The Future Forum,a non-profit organization established last year in Beijing,announced that pathologist Dennis Ming Yuk Lo from the Chinese University of Hong Kong won the life sciences Future Science Prize for the discovery of fetal cell-free DNA（cfDNA）in maternal plasma in 1997（Lo et al.,1997）.By detecting male fetus-derived Y sequences in maternal plasma,Lo et al.successfully proved the presence of fetal cfDNA in maternal plasma and serum（Lo et al.,1997）.展开更多
基金supported by the National Institutes of Health grants EY034116 (to WKJ, KYK, and SHC) and AG081037 (to YIM and WKJ)。
文摘Glaucoma is a multifactorial eye disorder that can cause vision loss and irreversible blindness,affecting individ uals aged 40 to 80 yea rs worldwide.Due to the aging population,it is expected that the number of people affected by glaucoma will surpass 111 million by 2040 as the disease becomes more prevalent.Glaucoma primarily contributes to optic nerve axon loss and the progressive degeneration of retinal ganglion cells (RGCs),subsequently leading to vision impairment.
基金Supported by Research to Prevent Blindness,New York,NY,USA。
文摘AIM:To determine the amount of ultraviolet(UV)light irradiance that various layers of the eye receive as sunlight passes through the eye,and to investigate the protective benefits of UV light-blocking contact lenses.METHODS:Twenty-four porcine eyes were prepared in one of three ways:isolated cornea,cornea and lens together,or whole eye preparation.UV light irradiance was measured with a UV-A/B light meter before and after the eye preparations were placed over the meter to measure UV light penetration in each eye structure.In the whole eye preparation,a hole was placed in the fovea to measure light as it passed through the vitreous.Subsequently,UVprotective contact lenses were placed over the structures,and UV light penetrance was measured.Measurements of UV light exposure were taken outdoors at various locations and times.RESULTS:Cornea absorbed 63.56%of UV light that reached the eye.Cornea and lens absorbed 99.34%of UV light.Whole eye absorbed 99.77%of UV light.When UV-protective contact lenses were placed,absorption was 98.90%,99.55%,and 99.87%,respectively.UV light exposure was dependent on directionality and time of day,and was greatest in areas of high albedo that reflect significant amounts of light,such as a beach.CONCLUSION:Cornea absorbs the majority of UV light that reaches the eye in this model.UV-protective contact lenses reduce UV exposure to the eye.Locations with high albedo expose the eye to higher levels of UV light.
文摘AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths(ALs) at one United States Veterans Affairs teaching hospital.METHODS: A retrospective chart review was conducted from November 2013 to May 2018. One eye of each patient who underwent cataract surgery with a monofocal intraocular lens(IOL) was included. The range of postoperative follow-up period was from 3 wk to 4 mo. The Holladay 2, Barrett Universal II, and Hill-Radial Basis Function(Hill-RBF) formulae were used to predict the postoperative refraction for all cataract surgeries. For each formula, we calculated the prediction errors [including mean absolute prediction error(MAE)] and the percentage of eyes within ±0.25 diopter(D) and ±0.5 D of predicted refraction. We performed subgroup analyses for short(AL<22.0 mm), medium(AL 22.0-25.0 mm), and long eyes(AL>25.0 mm).RESULTS: A total of 1131 patients were screened, and 909 met the inclusion criteria. Resident ophthalmologists were the primary surgeons in 710(78.1%) cases. We found no statistically significant difference in predictive accuracy among the three formulae over the entire AL range or in the short, medium, and long eye subgroups. Across the entire AL range, the Hill-RBF formula resulted in the lowest MAE(0.384 D) and the highest percentage of eyes with postoperative refraction within ±0.25 D(42.7%) and ±0.5 D(75.5%) of predicted. All three formulae had the highest MAEs(>0.5 D) and lowest percentage within ±0.5 D of predicted refraction(<55%) in short eyes.CONCLUSION: In cataract surgery patients at our teaching hospital, three commonly used biometric formulae demonstrate similar refractive accuracy across all ALs. Short eyes pose the greatest challenge to predicting postoperative refractive error.
文摘Oxidative stress and cyclic adenosine 3′,5′-monophosphate(cAMP)/protein kinase A(PKA)pathway in the optic nerve head astrocytes:Glaucoma is a leading cause of blindness worldwide in individuals 60 years of age and older.Despite the widely appreciated disease relevance of structural and functional abnormalities of astrocyte in the optic nerve head(ONH)that is associated with retinal ganglion cell(RGC)axon degeneration,the molecular mechanisms underlying astrocyte dysfunction in glaucomatous ONH degeneration are poorly understood.Oxidative stress is strongly linked to glaucoma pathogenesis,and astrocytes are the responsible cell type that is mostly related to oxidative stress and glaucomatous ONH degeneration.
文摘Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD includes soft drusen and pigmentary changes in the retinal pigment epithelium (RPE). As people age, such soft confluent drusen can progress into two forms of advanced AMD, geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD) and result in the loss of central vision. The exact mechanism for developing early AMD and progressing to advanced stage of disease is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as the cause of AMD progression. Together, complement factor H (CFH) and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress from activities such as smoking has also demonstrated a powerful contribution to AMD progression. To extend our previous finding that genetic polymorphisms in CFH results in OxPLs and the risk-form of CFH (CFH Y402H) has reduced affinity for oxidized phospholipids, and subsequent diminished capacity which subsequently diminishes the capability to attenuate the inflammatory effects of these molecules, we compared the binding properties of CFH and CFH related protein 1 (CFHR1), which is also associated with disease risk, to OxPLs and their effects on modulating inflammation and lipids uptake. As both CFH-402H and CFHR1 are associated with increased risk to AMD, we hypothesized that like CFH-402H, CFHR1 contribution to AMD risk may also be due to its diminished affinity for OxPLs. Interestingly, we found that association of CFHR1 with OxPLs was not statistically different than CFH. However, binding of CFHR1 did not elicit the same protective benefits as CFH in that both inflammation and lipid uptake are unaffected by CFHR1 association with OxPLs. These findings demonstrate a novel and interesting complexity to the potential interplay between the complement system and oxidative stress byproducts, such as OxPLs, in the mechanistic contribution to AMD. Future work will aim to identify the molecular distinctions between CFH and CFHR1 which confer protection by the former, but not latter molecules. Understanding the molecular domains necessary for protection could provide interventional insights in the generation of novel therapeutics for AMD and other diseases associated with oxidative stress.
基金Supported by the National Natural Science Foundation of China(No.82070955)the Science and Technology Program of Guangzhou(2022),China(No.202201020362)the High-level Hospital Construction Project,Zhongshan Ophthalmic Center,Sun Yat-sen University(No.303020104)。
文摘AIM:To evaluate the safety and efficacy of posterior scleral application(a modified technique)of an antimetabolite mitomycin C-soaked sponge in trabeculectomy for patients with glaucoma.METHODS:This retrospective study included 101 patients(115 eyes)with glaucoma(aged 12–83y)who underwent trabeculectomy using a modified mitomycin C-soaked sponge placement method.A piece of 3.5×10 mm2 sponge was placed vertically and posteriorly with the long side perpendicular to the limbus.The mitomycin C concentration and exposure time were 0.2–0.5 mg/m L and 1–5min,respectively.Intraocular pressure,bestcorrected visual acuity,and hypotensive medications were recorded at baseline and at the final visit.Complications,interventions required,and bleb morphology were recorded postoperatively.The primary outcome was trabeculectomy safety,including complications and bleb morphology;the secondary outcome was the trabeculectomy success rate.RESULTS:At the final follow-up[median 28mo,range 7–67mo and interquartile range(IQR)13mo],the qualified(cumulative)success rate was 93.0%and the complete success rate was 60.0%.No bleb-related complications were observed.The mean height,extent,and vascularity grades were 0.6±0.9,1.1±0.4,and 2.4±0.9,respectively.All Seidel tests were negative.The mean posteriority grade was 0.8±0.4.CONCLUSION:Trabeculectomy with the long side of a mitomycin C-soaked sponge placed perpendicular to the corneal limbus is safe and effective.
文摘Diabetic retinopathy(DR)is the most common microvascular complication in patients with diabetes mellitus(DM),and remains the single greatest cause of blindness in working age adults around the world.In this article,we review the evolution of pharmacotherapies for both diabetic macular edema(DME)and DR such as anti-vascular endothelial growth factor inhibitors and various steroid formulations,as well as other emerging pharmacotherapies currently in late stage clinical testing for this disease.
基金supported by Beijing New Star of Science and Technology (H020821380190, Z131102000413025)Fund of Work Committee for Women and Children of China State Department (2014108)+1 种基金National Natural Science Foundation (30471861)Beijing Institute of Ophthalmology Leading Programme (201515)
文摘The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental(OFCD)syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296 delT in exon4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.
文摘The human lens is composed anteriorly of a single layer of epithelial cells, which undergo mitosis and migrate to the lens equator where they differentiate into lens fiber cells [1]. The elongated lens fiber cells express high levels of soluble crystallin proteins that do not undergo turnover and must remain relatively stable over a lifetime. The three- dimensional organization of crystallins is crucial for lens transparency and refractive power and therefore visual acu- ity.
文摘Since the concept of signal transduction was introduced in the 1970s,various signal transduction pathways and signaling molecules have been identified.A major driving force in this field is the potential for signaling pathway-targeted therapy in clinical applications.
基金funded by research grants from the National Natural Science Foundation of China(Grants No.82122017,81870642,81970780,81670835,and 81700819)Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission(Grants No.19441900700 and 21S31904900)Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(Grants No.SHDC12019X08 and SHDC2020CR4078)。
文摘Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.
基金supported by the National Natural Science Foundation of China (81271005 and 81300767)Beijing Natural Science Foundation (7122038)Capital Health Research and Development of Special Foundation (ZYLX201501)。
文摘Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema,which is the leading hypothesis of acute mountain sickness(AMS).However,studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature.This study aimed to investigate ocular microcirculation alterations,the only visualized capillaries in the central neural system(CNS),during early-stage AMS using a hypobaric chamber.This study found that after high altitude simulation,the optic nerve showed retinal nerve fiber layer thickening(P=0.004–0.018)in some locations,and the area of the optic nerve subarachnoid space(P=0.004)enlarged.Optical coherence tomography angiography(OCTA)showed increased retinal radial peripapillary capillary(RPC)flow density(P=0.003–0.046),particularly on the nasal side of the nerve.The AMSpositive group had the largest increases in RPC flow density in the nasal sector(AMS-positive,?3.21±2.37;AMS-negative,?0.01±2.16,P=0.004).Among multiple ocular changes,OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms(beta=0.222,95%CI,0.009–0.435,P=0.042).The area under the receiver operating characteristics curve(AUC)for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882(95%CI,0.746–0.998).The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS.RPC OCTA endpoints may serve as a rapid,noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes.
基金supported in part by National Institutes of Health grants 1RM1HG009491,HG008135,EY025090,and CA217642。
文摘Age-related Macular Degeneration(AMD)is a leading cause of blindness in the developed world,especially in aging populations,and is therefore an important target for new therapeutic development.Recently,there have been several studies demonstrating strong associations between AMD and sites of heritable genetic variation at multiple loci,including a highly significant association at 10q26.The 10q26 risk region contains two genes,HTRA1 and ARMS2,both of which have been separately implicated as causative for the disease,as well as dozens of sites of non-coding variation.To date,no studies have successfully pinpointed which of these variant sites are functional in AMD,nor definitively identified which genes in the region are targets of such regulatory variation.In order to efficiently decipher which sites are functional in AMD phenotypes,we describe a general framework for combinatorial assembly of large‘synthetic haplotypes’along with delivery to relevant disease cell types for downstream functional analysis.We demonstrate the successful and highly efficient assembly of a first-draft 119kb wild-type‘assemblon’covering the HTRA1/ARMS2 risk region.We further propose the parallelized assembly of a library of combinatorial variant synthetic haplotypes covering the region,delivery and analysis of which will identify functional sites and their effects,leading to an improved understanding of AMD development.We anticipate that the methodology proposed here is highly generalizable towards the difficult problem of identifying truly functional variants from those discovered via GWAS or other genetic association studies.
基金The study was partially supported by NSFC(81300778,81271020)973 program(2012CB917304)+1 种基金863 Program(2014AA021604)NIH(R01EY024134,R01HG008135,R01EY018660,R01EY021374)and VA Merit Award.
文摘Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD.We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status.Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages.The algorithm could also be potentially applied for therapeutic response,and toward personalized care and precision medicine.
基金Henan Science Fund for Distinguished Young Scholars,Grant/Award Number:212300410020National Natural Science Foundation of China,Grant/Award Numbers:U22A2077,11974317Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2022MH280。
文摘Advanced sustainable biomedical materials are urgently needed for clinical applications;however,developing biomedical materials with exceptional mechanical and bactericidal properties as well as removable functionalities to reduce unintended secondary injury remains a challenge.Here,we report a biomass-derived composite consisting of water-soluble fish gelatin(FG)and antibacterial ZnO@silk fibroin(ZSF)microspheres for potential application as the wound dressing.The ZSF microspheres are embedded in a FG matrix to realize the stretchable,antibacterial,and removable ZSF/FG composites.By introducing glycerin as the plasticizer,ZSF/FG composites deliver a tensile strength of 4.5 MPa and stretchability of 550%.Acting as both the germicide and hydrophile components,ZSF microspheres endow the composites with excellent antibacterial capacity and water solubility.To prevent secondary injury,the ZSF/FG composites can be easily removed from the wounds by simply exposing them to excess water.Additionally,the ZSF/FG composites exhibit favorable biocompatibility and sustain high cell viability of over 100%.The full-thickness skin wound model on infected mice demonstrated an efficient rate of wound closure and a reduced inflammatory response.The ZSF/FG composite shows promise to hasten the healing of infected wounds and is expected a promising candidate as wound dressing for clinical therapy.
文摘Retinal degenerative diseases are a major cause of blindness.Retinal gene therapy is a trail-blazer in the human gene therapy field,leading to the frst FDA approved gene therapy product for a human genetic disease.The application of Clustered Regularly Interspaced Short Palindromic Repeat/Cas9(CRISPR/Cas9)-mediated gene editing technology is transforming the delivery of gene therapy.We review the history,present,and future pro-spects of retinal gene therapy.
文摘The Future Forum,a non-profit organization established last year in Beijing,announced that pathologist Dennis Ming Yuk Lo from the Chinese University of Hong Kong won the life sciences Future Science Prize for the discovery of fetal cell-free DNA（cfDNA）in maternal plasma in 1997（Lo et al.,1997）.By detecting male fetus-derived Y sequences in maternal plasma,Lo et al.successfully proved the presence of fetal cfDNA in maternal plasma and serum（Lo et al.,1997）.
