Progress in Retinal and Eye Research最新文献

{"title":"The versatile roles of retinal pigment epithelium in the pathophysiology of retinitis pigmentosa","authors":"Hanaa Ghanawi,&nbsp;Susanne F. Koch","doi":"10.1016/j.preteyeres.2025.101390","DOIUrl":"10.1016/j.preteyeres.2025.101390","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is a group of hereditary retinal diseases that lead to progressive vision loss, with most disease-causing genes expressed in rod photoreceptors and a smaller fraction in retinal pigment epithelium (RPE) cells. The RPE and photoreceptor cells share a symbiotic relationship characterized by close spatial and functional interactions that play a pivotal role in vision. Although the role of RPE is fundamental to the retina, its involvement in retinal pathogenesis, and, in particular, in RP remains underappreciated. In this review, we summarize morphological alterations in the RPE resulting from pathogenic mutations specific to RPE cells, as well as those occurring secondary to photoreceptor degeneration. We provide a comprehensive summary of how mutations in RPE-specific genes play a key role in the pathophysiology of RP. Finally, we discuss the latest therapeutic approaches, including AAV-mediated gene augmentation, RPE cell transplantation, and pharmacological interventions.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101390"},"PeriodicalIF":18.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650226","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}

{"title":"Replacing the vitreous body with hydrogels: Rationale and strategies","authors":"André Schulz ,&nbsp;Meghal Keskar ,&nbsp;Katelyn E. Swindle-Reilly ,&nbsp;Valentin Junge ,&nbsp;Bhav Harshad Parikh ,&nbsp;Xinyi Su ,&nbsp;Zengping Liu ,&nbsp;Ivan Seah","doi":"10.1016/j.preteyeres.2025.101389","DOIUrl":"10.1016/j.preteyeres.2025.101389","url":null,"abstract":"<div><div>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 <em>in-situ</em> 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.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101389"},"PeriodicalIF":18.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144613298","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}

{"title":"Bisretinoid lipofuscin, fundus autofluorescence and retinal disease","authors":"Janet R. Sparrow ,&nbsp;Hye Jin Kim","doi":"10.1016/j.preteyeres.2025.101388","DOIUrl":"10.1016/j.preteyeres.2025.101388","url":null,"abstract":"<div><div>Retinal pigment epithelium emits an inherent autofluorescence that originates from naturally occurring fluorophores when excited by short-wavelength light (SW-AF) in the spectral range between 400 and 590 nm. Peak excitation is 490 nm. The autofluorescence emission occurs at wavelengths between 520 and 800 nm with a peak of approximately 600 nm. For clinical purposes this emission is recorded as fundus autofluorescence either using a confocal scanning laser ophthalmoscope (cSLO; 488 nm excitation); a modified fundus camera or by ultra-wide-field ophthalmoscopic technology. The topographic distribution and intensities of fundus autofluorescence are modulated by superior-inferior differences in retinal illuminance. The autofluorescence distribution also departs from normal in the presence of retinal disease; accordingly these changing patterns assist in the diagnosis and monitoring of the disorders. The cellular source of SW-AF is consistent with an origin from a group of di-retinaldehyde (bisretinoid fluorophores) compounds that are produced randomly in photoreceptor cells and constitute the lipofuscin of the retinal pigment epithelium. Bisretinoids also contribute to retinal disease processes. Here we will primarily address this family of bisretinoid fluorophores since they account for the spectral, age- and disease-related properties of retina lipofuscin and SW-AF. Moreover, the differing absorbances exhibited by the members of this group of fluorophores accounts for the range of excitation wavelengths that elicit fluorescence emission from RPE lipofuscin and from the fundus. That range is consistent with emission from a family of fluorophores, not a single fluorophore.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101388"},"PeriodicalIF":18.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604931","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}

{"title":"Phenotyping and genotyping FEVR: Molecular genetics, clinical and imaging features, and therapeutics","authors":"You Wang ,&nbsp;Xinyu Liu ,&nbsp;Wenjia Yan ,&nbsp;Yizhe Cheng ,&nbsp;Aohan Hou ,&nbsp;Linyan Zhang ,&nbsp;Jinglin Lu ,&nbsp;Miner Yuan ,&nbsp;Yanting Lai ,&nbsp;Zhenglin Yang ,&nbsp;Xiaoxin Li ,&nbsp;Xiaoyan Ding","doi":"10.1016/j.preteyeres.2025.101387","DOIUrl":"10.1016/j.preteyeres.2025.101387","url":null,"abstract":"<div><div>Familial exudative vitreoretinopathy (FEVR) is a genetically complex retinal vascular disorder, often manifesting in infancy or early childhood, and characterized by peripheral retinal avascularity, neovascularization, and retinal detachment. The disease, predominantly inherited in an autosomal dominant manner, is associated with mutations in genes such as <em>LRP5, FZD4,</em> and <em>TSPAN12</em>, which disrupt the Wnt/β-catenin and Norrin signaling pathways, critical for retinal vascular development. FEVR's clinical spectrum ranges from asymptomatic cases to severe vision loss, making early diagnosis and intervention essential for preserving sight. Management strategies include laser photocoagulation, anti-VEGF therapy, and surgery, tailored to disease stage and patient age. The future of FEVR treatment lies in predictive genetics, early screening, and proactive therapy. Ongoing research into the molecular mechanisms of FEVR offers the potential for transforming this progressive disease into a preventable one, improving outcomes for affected individuals.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101387"},"PeriodicalIF":18.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584706","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}

{"title":"Corrigendum to “Glands of Moll: history, current knowledge and their role in ocular surface homeostasis and disease” [Progr. Retin. Eye Res. 106 (2025) 101362]","authors":"Michael Stopfer ,&nbsp;Ingrid Zahn ,&nbsp;Katharina Jüngert ,&nbsp;Gerhard Aumüller ,&nbsp;Frans L. Moll ,&nbsp;Martin Schicht ,&nbsp;Helen P. Makarenkova ,&nbsp;Cintia S. de Paiva ,&nbsp;Friedrich P. Paulsen","doi":"10.1016/j.preteyeres.2025.101364","DOIUrl":"10.1016/j.preteyeres.2025.101364","url":null,"abstract":"","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101364"},"PeriodicalIF":18.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120661","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}

{"title":"Immunomodulatory therapy in non-infectious Uveitis: Current landscape, gaps, and future directions","authors":"Rupesh Agrawal ,&nbsp;Yun Yao Goh ,&nbsp;William Rojas-Carabali ,&nbsp;Carlos Cifuentes-González ,&nbsp;Sanjay Srinivasan ,&nbsp;Bernard Yu-Hor Thong ,&nbsp;Alejandra de-la-Torre ,&nbsp;Cesar Michael Samson ,&nbsp;Jyotirmay Biswas ,&nbsp;Robert Patrick Finger ,&nbsp;John H. Kempen","doi":"10.1016/j.preteyeres.2025.101380","DOIUrl":"10.1016/j.preteyeres.2025.101380","url":null,"abstract":"<div><div>Non-infectious uveitis (NIU) is a potentially sight-threatening intraocular inflammatory condition that may arise idiopathically or in association with systemic immune-mediated diseases. While corticosteroids remain essential for rapid suppression of inflammation, their long-term use is limited by significant systemic and ocular side effects. Thus, immunomodulatory therapy (IMT)—including antimetabolites, calcineurin inhibitors, biologics, and emerging small molecules—has become central to achieving sustained control with a reduced corticosteroid burden in chronic cases.</div><div>Despite a range of therapeutic options, significant challenges persist. Safe, remission-inducing treatments remain elusive; tapering strategies are poorly standardized; and evidence for optimal combinations or long-term outcomes remains limited. Recent registries, such as Programme for Ocular Inflammation and Infection Translational Research (PROTON) and Treatment Exit Options for Uveitis (TOFU), are beginning to address the unmet need for structured treatment exit frameworks. Moreover, advances in imaging and artificial intelligence may soon enable real-time monitoring of disease status and risk stratification, although the development of large, well-annotated cohorts to be subject to such analysis remains a key hurdle.</div><div>This review summarizes the current role of IMT in the management of NIU, with an emphasis on corticosteroid-sparing strategies. We highlight the use of conventional immunosuppressants—including antimetabolites, calcineurin inhibitors, and alkylating agents—as well as newer biologic, smallmolecule, and interferon-based therapies. We outline where IMT fits within the broader treatment algorithm, discuss emerging evidence for earlier initiation, and explore future directions in targeted and personalized immunotherapy. We also explore future directions, including personalized approaches, biomarker-driven therapy, and the promise of AI-guided prediction models.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"108 ","pages":"Article 101380"},"PeriodicalIF":18.6,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335476","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}

{"title":"Widefield OCT angiography","authors":"Yali Jia ,&nbsp;Tristan T. Hormel ,&nbsp;Thomas S. Hwang ,&nbsp;An-Lun Wu ,&nbsp;Guangru B. Liang ,&nbsp;Yukun Guo ,&nbsp;Xiang Wei ,&nbsp;Shuibin Ni ,&nbsp;Yifan Jian ,&nbsp;J. Peter Campbell ,&nbsp;Steven T. Bailey ,&nbsp;John C. Morrison ,&nbsp;David Huang","doi":"10.1016/j.preteyeres.2025.101378","DOIUrl":"10.1016/j.preteyeres.2025.101378","url":null,"abstract":"<div><div>Optical coherence tomography angiography (OCTA) is a volumetric, non-invasive, high-resolution vascular imaging modality capable of acquiring highly detailed visualizations of retinal microvasculature. It has become an important tool for diagnosis and prognosis in prevalent diseases and pathologies such as diabetic retinopathy, retinopathy of prematurity, and vein occlusions, as well as more rare conditions, including inherited retinal dystrophies. It is also useful for measuring treatment response and assessing which patients would benefit from treatment. Unlike dye-based angiography, OCTA eliminates risks such as anaphylaxis. It also often outperforms fundus photography in feature detection. However, conventional OCTA imaging has been limited by its small field of view, which restricts simultaneous visualization of the posterior pole and peripheral retina, causing single images to potentially miss widely spaced critical biomarkers and pathological features. Recent technological advances in widefield OCTA have addressed this limitation, extending the field of view to the mid-periphery and beyond. This breakthrough enhances the simultaneous detection of macular and peripheral retinal pathology and significantly broadens OCTA's diagnostic and research applications. This review explores the technical innovations enabling widefield OCTA and highlights its clinical utility across various conditions, emphasizing its growing importance as a powerful tool in ophthalmic practice and research.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101378"},"PeriodicalIF":18.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289814","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}

{"title":"Understanding glaucoma as astrocyte-driven neurodegeneration in the optic nerve head: an integrative clinicopathological perspective","authors":"Eun Jung Lee ,&nbsp;Do Young Park ,&nbsp;Jong Chul Han ,&nbsp;Changwon Kee","doi":"10.1016/j.preteyeres.2025.101379","DOIUrl":"10.1016/j.preteyeres.2025.101379","url":null,"abstract":"<div><div>Glaucoma is characterized by the progressive loss of retinal ganglion cells (RGCs), primarily driven by axonal degeneration within the optic nerve head (ONH). Recent advances in neurodegeneration and neuroinflammation research have opened new astrocyte-centered perspectives on glaucoma pathogenesis. Critical evaluation of emerging evidence suggests that ONH astrocyte changes may serve as the primary driver of pathogenesis, with loss of astrocytic support playing a substantial role. Evidence from experimental glaucoma models reveals that early intraocular pressure (IOP)-induced remodeling of the ONH astrocyte network precedes RGC axonal damage, potentially mediated by impaired astrocytic control of electrophysiological homeostasis within the surrounding extracellular space. <span>Furthermore</span>, the heterogeneous glia-neuron ratio (GNR) across the normal human ONH lamina cribrosa exhibits an inverse topographic association with the spatiotemporal pattern of regional vulnerability observed clinically in glaucoma, suggesting that regional variations in the astrocyte-to-neuron ratio, reflecting astrocytic support reserve, may critically determine local tissue susceptibility to glaucomatous stress. Recent optical coherence tomography–based insights into the regional vulnerability in human glaucoma are discussed. This clinicopathological interpretation may offer a comprehensive framework that coherently integrates diverse neurodegenerative mechanisms into a unified clinical entity, bridge the conventional mechanical and ischemic theories of glaucoma by highlighting astrocyte changes as a common primary target of risk factors, and ultimately redefine glaucoma as astrocyte-driven neurodegeneration in the biomechanically and bioenergetically vulnerable ONH.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101379"},"PeriodicalIF":18.6,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144289813","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}

{"title":"Shining light on CRISPR/Cas9 therapeutics for inherited retinal diseases","authors":"A.B. Geiger ,&nbsp;J.G. Kennedy ,&nbsp;L.G. Staker ,&nbsp;T.G. Wensel ,&nbsp;R.J. Casson ,&nbsp;P.Q. Thomas","doi":"10.1016/j.preteyeres.2025.101376","DOIUrl":"10.1016/j.preteyeres.2025.101376","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs), such as retinitis pigmentosa, are a heterogenous group of genetic eye diseases characterized by degeneration of photoreceptors. They are the leading cause of blindness in the working age population in high-income countries and are an ideal target for the expanding gene editing tool kit, including rapidly evolving CRISPR/Cas9 technology. In this review, we provide a comprehensive analysis of CRISPR/Cas9 technologies currently being explored as therapeutic interventions for IRDs. Given the challenges posed by the growing complexity and size of gene editing systems, the delivery of these therapeutics to the retina has necessitated innovative approaches. We review current delivery methods, including nanoparticles, virus-like particles and traditional viral vectors, highlighting their advantages and limitations. This review underscores the potential transformative impact of gene editing on genetic disease management, emphasising that advancements in these technologies, coupled with improved pre-clinical models, bring clinically safe and effective treatments for IRDs within view.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101376"},"PeriodicalIF":18.6,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249422","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}

{"title":"Unravelling CYP4V2: Clinical features, genetic insights, pathogenic mechanisms and therapeutic strategies in Bietti crystalline corneoretinal dystrophy","authors":"Ruixuan Jia ,&nbsp;Shaohong Chen ,&nbsp;Wang Li ,&nbsp;Jinlu Zhang ,&nbsp;Baoyuan Qu ,&nbsp;Jing Qiao ,&nbsp;Xiang Meng ,&nbsp;Shicheng Yu ,&nbsp;Xiaozhen Liu ,&nbsp;Boling Xu ,&nbsp;Tianjin Chen ,&nbsp;Xiuping Shen ,&nbsp;Wenmin Sun ,&nbsp;Hongliang Dou ,&nbsp;Vinit B. Mahajan ,&nbsp;Qiongjiong Zhang ,&nbsp;Liping Yang","doi":"10.1016/j.preteyeres.2025.101377","DOIUrl":"10.1016/j.preteyeres.2025.101377","url":null,"abstract":"<div><div>Inherited retinal dystrophies (IRDs) comprise a spectrum of disease phenotypes with genetic heterogeneity and clinical phenotypic diversity. Bietti crystalline corneoretinal dystrophy (BCD) represents a distinct IRD subtype characterized by crystalline deposits in the retina. Although rare in Western populations, BCD ranks among the most prevalent IRDs in East Asia, affecting an estimated 124,000 to 377,000 individuals worldwide. As a severe type of IRD, BCD demonstrates accelerated progression and currently lacks effective treatment. The BCD disease is caused by a biallelic mutation in the <em>CYP4V2</em> gene. With a coding sequence (CDS) of 1,578 bp, <em>CYP4V2</em> can be effectively encapsulated into adeno-associated virus (AAV) vectors. As a hydroxylase, CYP4V2 is mainly expressed in retinal pigment epithelial (RPE) cells, which can be transduced by AAVs and are suitable for gene augmentation therapy that replaces the function of mutant proteins. Given the large patient population, severe visual impairment, and feasibility of gene therapy, several research groups are interested in developing gene therapy products for BCD, and two products entering Phase III clinical trials have made significant progress. This review outlines the clinical features, genetic insights and pathogenic mechanisms of BCD and discusses the ongoing gene therapy clinical trials, including efficacy and concerns. This knowledge will help us bridge the gap between molecular studies and clinical treatments, facilitating translation from bench to bedside. We believe that advancements in BCD gene therapy will inform the treatment of other IRDs.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101377"},"PeriodicalIF":18.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144242655","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}