Pub Date : 2025-11-01Epub Date: 2025-09-19DOI: 10.1016/j.preteyeres.2025.101404
Brian S. McKay , Andreas M. Grabrucker , Richard B. Thompson , Emily Y. Chew , Imre Lengyel , Héctor González-Iglesias
Zinc is an essential trace mineral that plays a crucial role in numerous bodily functions, including immune response, wound healing, and protein synthesis. Regarding eye health, zinc is particularly important due to its high concentration, functional abundance, and critical roles in the retina/RPE/choroid complex, where both deficiency and excess can lead to cellular dysfunction. This mineral contributes significantly to the maintenance of the structure and function of the tissues, and it is believed to help protect against oxidative stress, which can damage cells in the eye. The retinal pigment epithelium/choroid complex (RPE/choroid) contains the highest zinc concentration. Therefore, it is unsurprising that several eye disorders associated with this interface are associated with reduced zinc accumulation, and zinc supplementation has become an essential secondary preventive therapy for diseases like age-related macular degeneration (AMD). Despite zinc's importance in health and diseases of the outer retina, it still needs to be fully understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. However, it appears that adequate zinc levels are essential for retinal health and overall vision, particularly as we age. This review is focused on summarising our current understanding of the biology of zinc, with particular attention paid to the RPE/choroid interface.
{"title":"Zinc in eye health, retinal biology and disease","authors":"Brian S. McKay , Andreas M. Grabrucker , Richard B. Thompson , Emily Y. Chew , Imre Lengyel , Héctor González-Iglesias","doi":"10.1016/j.preteyeres.2025.101404","DOIUrl":"10.1016/j.preteyeres.2025.101404","url":null,"abstract":"<div><div>Zinc is an essential trace mineral that plays a crucial role in numerous bodily functions, including immune response, wound healing, and protein synthesis. Regarding eye health, zinc is particularly important due to its high concentration, functional abundance, and critical roles in the retina/RPE/choroid complex, where both deficiency and excess can lead to cellular dysfunction. This mineral contributes significantly to the maintenance of the structure and function of the tissues, and it is believed to help protect against oxidative stress, which can damage cells in the eye. The retinal pigment epithelium/choroid complex (RPE/choroid) contains the highest zinc concentration. Therefore, it is unsurprising that several eye disorders associated with this interface are associated with reduced zinc accumulation, and zinc supplementation has become an essential secondary preventive therapy for diseases like age-related macular degeneration (AMD). Despite zinc's importance in health and diseases of the outer retina, it still needs to be fully understood how zinc participates in cellular and molecular events and how zinc supplementation might be beneficial. However, it appears that adequate zinc levels are essential for retinal health and overall vision, particularly as we age. This review is focused on summarising our current understanding of the biology of zinc, with particular attention paid to the RPE/choroid interface.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101404"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145113590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-11-12DOI: 10.1016/j.preteyeres.2025.101413
Marina Gorbatyuk , Nishant R. Sinha , Rajnish Kumar , Assylbek Zhylkibayev , Mohammad Athar , Patrick McNutt , Rajiv R. Mohan
Vesicants, powerful chemical weapons of mass destruction, are agents that cause blistering of the skin and blindness upon accidental exposure or during warfare. In addition, their exposure induces a wide range of other symptoms, including those affecting the respiratory tract, digestive system, skin, and ocular tissues. The ocular tissue can be exposed through both direct and indirect routes, such as direct contact with the affected corneal tissue and systemic blood circulation. Investigating eye injuries caused by vesicants is a critical and growing field of research in ophthalmology and ocular toxicology. In this review, we present the current status of the research, covering significant advances made in the study of vesicant-induced corneal and retinal injuries. We also provide general information on vesicants and discuss animal models used to investigate the molecular mechanisms of vesicant exposure and to develop medical countermeasures. Finally, we identify gaps in the current knowledge of the molecular mechanisms of vesicant action and highlight future directions for this emerging field.
{"title":"Current progress in research on ocular injury caused by exposure to vesicants","authors":"Marina Gorbatyuk , Nishant R. Sinha , Rajnish Kumar , Assylbek Zhylkibayev , Mohammad Athar , Patrick McNutt , Rajiv R. Mohan","doi":"10.1016/j.preteyeres.2025.101413","DOIUrl":"10.1016/j.preteyeres.2025.101413","url":null,"abstract":"<div><div>Vesicants, powerful chemical weapons of mass destruction, are agents that cause blistering of the skin and blindness upon accidental exposure or during warfare. In addition, their exposure induces a wide range of other symptoms, including those affecting the respiratory tract, digestive system, skin, and ocular tissues. The ocular tissue can be exposed through both direct and indirect routes, such as direct contact with the affected corneal tissue and systemic blood circulation. Investigating eye injuries caused by vesicants is a critical and growing field of research in ophthalmology and ocular toxicology. In this review, we present the current status of the research, covering significant advances made in the study of vesicant-induced corneal and retinal injuries. We also provide general information on vesicants and discuss animal models used to investigate the molecular mechanisms of vesicant exposure and to develop medical countermeasures. Finally, we identify gaps in the current knowledge of the molecular mechanisms of vesicant action and highlight future directions for this emerging field.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101413"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145509651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
pediatric inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive visual function impairment, often manifesting from early childhood. These conditions arise from dysfunction in retinal morphogenesis, phototransduction, and cellular maintenance pathways, involving photoreceptors, the retinal pigment epithelium, and glial systems. This review provides an integrated analysis of the molecular underpinnings, phenotypic variability, diagnostic advancements, and emerging therapeutic avenues for pediatric IRDs. By systematically retracing the literature and leveraging over a decade of laboratory experience, we dissect each major form of pediatric IRD—such as Leber congenital amaurosis, retinitis pigmentosa, Stargardt disease, achromatopsia, and syndromic entities like Usher and Bardet-Biedl syndromes—emphasizing genotype-phenotype correlations and shared pathogenic pathways. Additionally, we discuss next-generation sequencing, advanced bioinformatics, and AI-based diagnostics, along with gene therapy, genome editing, and emerging biotechnologies. By mapping IRDs to molecular networks through Cytoscape and functional genomics, we identify converging pathogenic mechanisms and therapeutic targets. This compendium aims to serve as a reference for clinicians, researchers, and genetic counselors navigating the evolving IRD landscape.
{"title":"Decoding pediatric inherited retinal dystrophies: Bridging genetic complexity and clinical heterogeneity","authors":"Domenico Mordà , Simona Alibrandi , Concetta Scimone , Carmela Rinaldi , Sergio Zaccaria Scalinci , Giorgia Abate , Rosalia D'Angelo , Antonina Sidoti , Luigi Donato","doi":"10.1016/j.preteyeres.2025.101405","DOIUrl":"10.1016/j.preteyeres.2025.101405","url":null,"abstract":"<div><div>pediatric inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive visual function impairment, often manifesting from early childhood. These conditions arise from dysfunction in retinal morphogenesis, phototransduction, and cellular maintenance pathways, involving photoreceptors, the retinal pigment epithelium, and glial systems. This review provides an integrated analysis of the molecular underpinnings, phenotypic variability, diagnostic advancements, and emerging therapeutic avenues for pediatric IRDs. By systematically retracing the literature and leveraging over a decade of laboratory experience, we dissect each major form of pediatric IRD—such as Leber congenital amaurosis, retinitis pigmentosa, Stargardt disease, achromatopsia, and syndromic entities like Usher and Bardet-Biedl syndromes—emphasizing genotype-phenotype correlations and shared pathogenic pathways. Additionally, we discuss next-generation sequencing, advanced bioinformatics, and AI-based diagnostics, along with gene therapy, genome editing, and emerging biotechnologies. By mapping IRDs to molecular networks through Cytoscape and functional genomics, we identify converging pathogenic mechanisms and therapeutic targets. This compendium aims to serve as a reference for clinicians, researchers, and genetic counselors navigating the evolving IRD landscape.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101405"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-24DOI: 10.1016/j.preteyeres.2025.101406
Danny S.C. Ng , Paisan Ruamviboonsuk , Rajendra S. Apte , Sanyam Bajimaya , Carmen K.M. Chan , Andrew Chang , Carol Y. Cheung , Shih-Jen Chen , Varun Chaudhary , Voraporn Chaikitmongkol , Jay Chhablani , Taraprasad Das , Suber S. Huang , Jost B. Jonas , Timothy Y.Y. Lai , Chi-Chun Lai , Jin Ma , Marion R. Munk , Raja Narayanan , Nishant V. Radke , Dennis S.C. Lam
Diabetic macular edema (DME) is the most common cause of vision-threatening diabetic retinopathy (VTDR) with an increasing prevalence tied to the global epidemic in diabetes. Despite significant advances, the management of DME remains a dynamic field with many unresolved controversies. Optical coherence tomography (OCT) allows objective assessment, however, correlation between vision and morphological changes can be inconsistent, causing disagreements on treatment strategies. DME is a complex disease with multifactorial pathophysiological pathways, leading to heterogenous treatment responses. There is a lack of standardized definition of treatment “non-response” and protocol for switching to second-line or adjuvant treatments. New anti-vascular endothelial growth factor (anti-VEGF) drugs and multi-targeted therapies seem to demonstrate improved durability, but long-term data is not yet available. Research in artificial intelligence (AI) is developing rapidly, however, rigorous appraisal of its reliability and generalizability are necessary before its implementation. Significant vision loss from DME in pregnant women, young children and elderly patients with systemic comorbidities are challenging conundrums. An international panel of experts (IPE) comprising 36 experts from 16 countries formulated and voted on the consensus statements in 5 key areas: 1) Diagnostic controversies around classification and imaging; 2) Treatment controversies; 3) Management paradigm between protocol-based and individualized approaches; 4) Emerging controversies in novel therapeutics and AI application, and 5) Special considerations for specific patient populations. There is an imminent need for mutual agreement on the best-possible approach to DME management in order to promote the optimal patient outcomes and to identify specific issues that require prioritization of resources and research.
{"title":"International consensuses and controversies on causes, diagnosis and management of diabetic macular edema (DME)","authors":"Danny S.C. Ng , Paisan Ruamviboonsuk , Rajendra S. Apte , Sanyam Bajimaya , Carmen K.M. Chan , Andrew Chang , Carol Y. Cheung , Shih-Jen Chen , Varun Chaudhary , Voraporn Chaikitmongkol , Jay Chhablani , Taraprasad Das , Suber S. Huang , Jost B. Jonas , Timothy Y.Y. Lai , Chi-Chun Lai , Jin Ma , Marion R. Munk , Raja Narayanan , Nishant V. Radke , Dennis S.C. Lam","doi":"10.1016/j.preteyeres.2025.101406","DOIUrl":"10.1016/j.preteyeres.2025.101406","url":null,"abstract":"<div><div>Diabetic macular edema (DME) is the most common cause of vision-threatening diabetic retinopathy (VTDR) with an increasing prevalence tied to the global epidemic in diabetes. Despite significant advances, the management of DME remains a dynamic field with many unresolved controversies. Optical coherence tomography (OCT) allows objective assessment, however, correlation between vision and morphological changes can be inconsistent, causing disagreements on treatment strategies. DME is a complex disease with multifactorial pathophysiological pathways, leading to heterogenous treatment responses. There is a lack of standardized definition of treatment “non-response” and protocol for switching to second-line or adjuvant treatments. New anti-vascular endothelial growth factor (anti-VEGF) drugs and multi-targeted therapies seem to demonstrate improved durability, but long-term data is not yet available. Research in artificial intelligence (AI) is developing rapidly, however, rigorous appraisal of its reliability and generalizability are necessary before its implementation. Significant vision loss from DME in pregnant women, young children and elderly patients with systemic comorbidities are challenging conundrums. An international panel of experts (IPE) comprising 36 experts from 16 countries formulated and voted on the consensus statements in 5 key areas: 1) Diagnostic controversies around classification and imaging; 2) Treatment controversies; 3) Management paradigm between protocol-based and individualized approaches; 4) Emerging controversies in novel therapeutics and AI application, and 5) Special considerations for specific patient populations. There is an imminent need for mutual agreement on the best-possible approach to DME management in order to promote the optimal patient outcomes and to identify specific issues that require prioritization of resources and research.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101406"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-10DOI: 10.1016/j.preteyeres.2025.101409
Kajal Agrawal , Ashley Shuen Ying Hong , Carlos Cifuentes-González , Vanitha Shyamili Kumar , William Rojas-Carabali , Shengjuan Zhang , Qingfeng Wang , Alejandra de-la-Torre , Marlies Gijs , Tejpal Gill , James T. Rosenbaum , Seesandra V. Rajagopala , Sapna Gangaputra , Alessandro Conforti , R Paul Ross , Peizeng Yang , Sunny Wong , Rupesh Agrawal
Non-infectious uveitis is a group of complex inflammatory eye diseases shaped by genetic susceptibility, immune dysregulation, and environmental cues. Among these, the mucosal microbiome—including gut, oral, and ocular surface microbial communities—has emerged as a key player in modulating systemic and ocular immune responses. Recent evidence supports a gut-eye axis wherein microbial dysbiosis alters intestinal barrier function, perturbs T cell homeostasis, and drives systemic immune activation that can breach ocular immune privilege. Specific taxa, such as Prevotella and Faecalibacterium, as well as microbial metabolites including short-chain fatty acids, have been implicated in promoting or mitigating ocular inflammation. Human leukocyte antigen (HLA) alleles, notably HLA-B27 and HLA-A29, influence both microbiome composition and disease phenotype, suggesting a gene–microbiome–immunity triad of interaction in uveitis pathogenesis. Drawing on insights from metagenomics, metabolomics, in vitro and in vivo experimental and murine models, this review delineates four key mechanisms—immune imbalance, antigenic mimicry, epithelial barrier disruption, and bacterial translocation—that underpin the key roles of microbiome in uveitis. We combine current literature and integrate findings from our research programs to highlight diagnostic and therapeutic opportunities. Microbiome-informed strategies, such as rational probiotic design, dietary modulation, and targeted microbial therapies, hold promise for complementing existing immunosuppressive regimens. Translating these insights into clinical practice requires robust multi-omic studies, longitudinal cohorts, mechanistic studies, and precision-guided intervention trials. By framing uveitis within a mucosal immunological context, this review proposes a future precision medicine roadmap for integrating microbiome science into ocular inflammatory disease management.
{"title":"Microbiome signatures and their role in uveitis: Pathogenesis, diagnostics, and therapeutic perspectives","authors":"Kajal Agrawal , Ashley Shuen Ying Hong , Carlos Cifuentes-González , Vanitha Shyamili Kumar , William Rojas-Carabali , Shengjuan Zhang , Qingfeng Wang , Alejandra de-la-Torre , Marlies Gijs , Tejpal Gill , James T. Rosenbaum , Seesandra V. Rajagopala , Sapna Gangaputra , Alessandro Conforti , R Paul Ross , Peizeng Yang , Sunny Wong , Rupesh Agrawal","doi":"10.1016/j.preteyeres.2025.101409","DOIUrl":"10.1016/j.preteyeres.2025.101409","url":null,"abstract":"<div><div>Non-infectious uveitis is a group of complex inflammatory eye diseases shaped by genetic susceptibility, immune dysregulation, and environmental cues. Among these, the mucosal microbiome—including gut, oral, and ocular surface microbial communities—has emerged as a key player in modulating systemic and ocular immune responses. Recent evidence supports a gut-eye axis wherein microbial dysbiosis alters intestinal barrier function, perturbs T cell homeostasis, and drives systemic immune activation that can breach ocular immune privilege. Specific taxa, such as <em>Prevotella</em> and <em>Faecalibacterium</em>, as well as microbial metabolites including short-chain fatty acids, have been implicated in promoting or mitigating ocular inflammation. Human leukocyte antigen (HLA) alleles, notably HLA-B27 and HLA-A29, influence both microbiome composition and disease phenotype, suggesting a gene–microbiome–immunity triad of interaction in uveitis pathogenesis. Drawing on insights from metagenomics, metabolomics, <em>in vitro and in vivo</em> experimental and murine models, this review delineates four key mechanisms—immune imbalance, antigenic mimicry, epithelial barrier disruption, and bacterial translocation—that underpin the key roles of microbiome in uveitis. We combine current literature and integrate findings from our research programs to highlight diagnostic and therapeutic opportunities. Microbiome-informed strategies, such as rational probiotic design, dietary modulation, and targeted microbial therapies, hold promise for complementing existing immunosuppressive regimens. Translating these insights into clinical practice requires robust multi-omic studies, longitudinal cohorts, mechanistic studies, and precision-guided intervention trials. By framing uveitis within a mucosal immunological context, this review proposes a future precision medicine roadmap for integrating microbiome science into ocular inflammatory disease management.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101409"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-08-20DOI: 10.1016/j.preteyeres.2025.101392
Olaf Dammann, Tora S. Morken, Steven E. Brooks, Alison Chu, Christiane E.L. Dammann, M. Elizabeth Hartnett, Brian K. Stansfield, David K. Wallace
We hypothesize that the major pathologies associated with the visual system in preterm infants, retinopathy of prematurity (ROP), cerebral visual impairment (CVI), and neurodevelopmental impairment (NDI), are unified by a common etio-pathogenesis involving intermittent and/or sustained systemic inflammation (ISSI). We refer to the resulting adverse visual outcomes (AVO) as “visuopathy of prematurity” (VOP). We present the published evidence supporting an etio-pathogenic paradigm centered around ISSI that begins before birth (early phase 1), is exacerbated in the newborn period (intermediate phase 2), and culminates in adverse visual and neurodevelopmental outcomes (late phase 3).
{"title":"Elements of visuopathy of prematurity are unified by intermittent or sustained systemic inflammation","authors":"Olaf Dammann, Tora S. Morken, Steven E. Brooks, Alison Chu, Christiane E.L. Dammann, M. Elizabeth Hartnett, Brian K. Stansfield, David K. Wallace","doi":"10.1016/j.preteyeres.2025.101392","DOIUrl":"10.1016/j.preteyeres.2025.101392","url":null,"abstract":"<div><div>We hypothesize that the major pathologies associated with the visual system in preterm infants, retinopathy of prematurity (ROP), cerebral visual impairment (CVI), and neurodevelopmental impairment (NDI), are unified by a common etio-pathogenesis involving intermittent and/or sustained systemic inflammation (ISSI). We refer to the resulting adverse visual outcomes (AVO) as “visuopathy of prematurity” (VOP). We present the published evidence supporting an etio-pathogenic paradigm centered around ISSI that begins before birth (early phase 1), is exacerbated in the newborn period (intermediate phase 2), and culminates in adverse visual and neurodevelopmental outcomes (late phase 3).</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101392"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-26DOI: 10.1016/j.preteyeres.2025.101407
Gordon L. Fain , M. Carter Cornwall
Exposure of the eye to bright bleaching light produces a large decrease in photoreceptor sensitivity, followed by a slow return during adaptation to darkness. Although much progress has been made understanding the nature of this phenomenon, particularly its biochemistry, less is known about the physiology of dark adaptation. In this review, we summarize the evidence for desensitization produced by photoproducts of bleaching, especially apo-opsin, that is opsin without bound chromophore. We describe the relationship between these studies and diseases such as vitamin A deprivation and congenital stationary night blindness; the effects of analogs of chromophore on photoreceptor sensitivity; and the roles of transducin, rhodopsin kinase, and arrestin. We review many specialized features of dark adaptation in cones, including the role of retinal G protein-coupled receptor (RGR) opsin. For both rod and cone dark adaptation, we summarize some of the principal uncertainties in our understanding. We hope our review will provide a guide to past work as well as an indicator of many possible areas of future research.
{"title":"The physiology of dark adaptation: Progress and future directions","authors":"Gordon L. Fain , M. Carter Cornwall","doi":"10.1016/j.preteyeres.2025.101407","DOIUrl":"10.1016/j.preteyeres.2025.101407","url":null,"abstract":"<div><div>Exposure of the eye to bright bleaching light produces a large decrease in photoreceptor sensitivity, followed by a slow return during adaptation to darkness. Although much progress has been made understanding the nature of this phenomenon, particularly its biochemistry, less is known about the physiology of dark adaptation. In this review, we summarize the evidence for desensitization produced by photoproducts of bleaching, especially apo-opsin, that is opsin without bound chromophore. We describe the relationship between these studies and diseases such as vitamin A deprivation and congenital stationary night blindness; the effects of analogs of chromophore on photoreceptor sensitivity; and the roles of transducin, rhodopsin kinase, and arrestin. We review many specialized features of dark adaptation in cones, including the role of retinal G protein-coupled receptor (RGR) opsin. For both rod and cone dark adaptation, we summarize some of the principal uncertainties in our understanding. We hope our review will provide a guide to past work as well as an indicator of many possible areas of future research.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101407"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-09-15DOI: 10.1016/j.preteyeres.2025.101400
Brian P. Hall , Sakshi Shiromani , Brian L. Vanderbeek , Sayantan Datta , Preston E. Girardot , Archeta Rajagopalan , John M. Nickerson , Jeffrey H. Boatright , Nieraj Jain
Pentosan polysulfate (PPS) maculopathy is a progressive, vision-threatening retinal disorder linked to prolonged use of PPS, a heparin-like sulfated polysaccharide prescribed for interstitial cystitis/bladder pain syndrome. Affected individuals often experience impaired dark adaptation and progressive central vision loss. Fundus imaging commonly reveals hyperpigmented macular clumps at the level of the retinal pigment epithelium (RPE), and a distinctive pattern of autofluorescence abnormality in the posterior fundus. This degenerative maculopathy may continue to progress even after drug cessation, with some patients developing macular atrophy years later.
While the underlying pathogenic mechanism remains unclear, mounting evidence supports a causal relationship between PPS use and the macular pathology. Studies have repeatedly demonstrated the strength of the association; the dose-response relationship; and the lack of confounding by indication. Furthermore, laboratory studies demonstrate that such a toxicity is biologically plausible, suggesting a direct toxicity to the RPE and/or choroid.
Given the widespread use of PPS over many decades, tens of thousands of individuals are already at risk for toxicity, with no known treatment available. However, screening rates remain low; prescribing rates continue to rise in certain regions; and novel applications for the drug, such as subcutaneous injection for osteoarthritis, are under clinical investigation. Consequently, there is a pressing need for increased recognition of PPS toxicity and further understanding of disease mechanisms. This review summarizes the clinical characteristics of PPS maculopathy, evaluates its public health impact, explores potential pathogenic mechanisms, and presents a compelling case for causality using clinical, laboratory, and epidemiological evidence.
{"title":"Pentosan polysulfate maculopathy: clinical considerations, pathobiology, and causality","authors":"Brian P. Hall , Sakshi Shiromani , Brian L. Vanderbeek , Sayantan Datta , Preston E. Girardot , Archeta Rajagopalan , John M. Nickerson , Jeffrey H. Boatright , Nieraj Jain","doi":"10.1016/j.preteyeres.2025.101400","DOIUrl":"10.1016/j.preteyeres.2025.101400","url":null,"abstract":"<div><div>Pentosan polysulfate (PPS) maculopathy is a progressive, vision-threatening retinal disorder linked to prolonged use of PPS, a heparin-like sulfated polysaccharide prescribed for interstitial cystitis/bladder pain syndrome. Affected individuals often experience impaired dark adaptation and progressive central vision loss. Fundus imaging commonly reveals hyperpigmented macular clumps at the level of the retinal pigment epithelium (RPE), and a distinctive pattern of autofluorescence abnormality in the posterior fundus. This degenerative maculopathy may continue to progress even after drug cessation, with some patients developing macular atrophy years later.</div><div>While the underlying pathogenic mechanism remains unclear, mounting evidence supports a causal relationship between PPS use and the macular pathology. Studies have repeatedly demonstrated the strength of the association; the dose-response relationship; and the lack of confounding by indication. Furthermore, laboratory studies demonstrate that such a toxicity is biologically plausible, suggesting a direct toxicity to the RPE and/or choroid.</div><div>Given the widespread use of PPS over many decades, tens of thousands of individuals are already at risk for toxicity, with no known treatment available. However, screening rates remain low; prescribing rates continue to rise in certain regions; and novel applications for the drug, such as subcutaneous injection for osteoarthritis, are under clinical investigation. Consequently, there is a pressing need for increased recognition of PPS toxicity and further understanding of disease mechanisms. This review summarizes the clinical characteristics of PPS maculopathy, evaluates its public health impact, explores potential pathogenic mechanisms, and presents a compelling case for causality using clinical, laboratory, and epidemiological evidence.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101400"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01Epub Date: 2025-10-14DOI: 10.1016/j.preteyeres.2025.101408
Yali Jia , Tristan T. Hormel , Thomas S. Hwang , An-Lun Wu , Guangru B. Liang , Yukun Guo , Xiang Wei , Shuibin Ni , Yifan Jian , J. Peter Campbell , Steven T. Bailey , John C. Morrison , David Huang
{"title":"Corrigendum to “Widefield OCT angiography” [Progress in Retinal and Eye Research. 107 (2025) 101378]","authors":"Yali Jia , Tristan T. Hormel , Thomas S. Hwang , An-Lun Wu , Guangru B. Liang , Yukun Guo , Xiang Wei , Shuibin Ni , Yifan Jian , J. Peter Campbell , Steven T. Bailey , John C. Morrison , David Huang","doi":"10.1016/j.preteyeres.2025.101408","DOIUrl":"10.1016/j.preteyeres.2025.101408","url":null,"abstract":"","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"109 ","pages":"Article 101408"},"PeriodicalIF":14.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01Epub Date: 2025-07-09DOI: 10.1016/j.preteyeres.2025.101389
André Schulz , Meghal Keskar , Katelyn E. Swindle-Reilly , Valentin Junge , Bhav Harshad Parikh , Xinyi Su , Zengping Liu , Ivan Seah
During vitreoretinal surgery, the vitreous body is removed and requires a suitable replacement to ensure ocular homeostasis, as the native vitreous does not regenerate. An ideal vitreous substitute should mimic the optical, mechanical, and biochemical properties of the natural vitreous while maintaining long-term biocompatibility. Currently, clinically used substitutes such as gases and silicone oils facilitate retinal reattachment but deviate significantly from the native vitreous, leading to complications such as cataract formation, increased intraocular pressure, and emulsification. Given these limitations, there is a growing interest in hydrogels as potential vitreous substitutes due to their similarity to the native vitreous. This review therefore aspires to provide a comprehensive and detailed overview of current knowledge on the structural and biochemical composition of the vitreous, the challenges associated with existing substitutes, and recent advancements in vitreous replacement technologies. Particular attention is given to preformed and in-situ forming hydrogels, based on biopolymers and synthetic polymers, discussing their chemical composition, diverse characteristics with regard to the multiple requirements for vitreous substitutes, and clinical applicability. Finally, future challenges and opportunities in developing an ideal vitreous substitute are highlighted, including vitreous substitutes as drug delivery systems as well as cellularized vitreous substitutes by combining advanced hydrogel systems with hyalocytes as vitreous cells to further replicate the versatile characteristics and functions of the native vitreous.
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