Progress in Retinal and Eye Research最新文献

{"title":"Eye on the horizon: The metabolic landscape of the RPE in aging and disease","authors":"David S. Hansman ,&nbsp;Jianhai Du ,&nbsp;Robert J. Casson ,&nbsp;Daniel J. Peet","doi":"10.1016/j.preteyeres.2024.101306","DOIUrl":"10.1016/j.preteyeres.2024.101306","url":null,"abstract":"<div><div>To meet the prodigious bioenergetic demands of the photoreceptors, glucose and other nutrients must traverse the retinal pigment epithelium (RPE), a polarised monolayer of cells that lie at the interface between the outer retina and the choroid, the principal vascular layer of the eye. Recent investigations have revealed a metabolic ecosystem in the outer retina where the photoreceptors and RPE engage in a complex exchange of sugars, amino acids, and other metabolites. Perturbation of this delicate metabolic balance has been identified in the aging retina, as well as in age-related macular degeneration (AMD), the leading cause of blindness in the Western world. Also common in the aging and diseased retina are elevated levels of cytokines, oxidative stress, advanced glycation end-products, increased growth factor signalling, and biomechanical stress – all of which have been associated with metabolic dysregulation in non-retinal cell types and tissues. Herein, we outline the role of these factors in retinal homeostasis, aging, and disease. We discuss their effects on glucose, mitochondrial, lipid, and amino acid metabolism in tissues and cell types outside the retina, highlighting the signalling pathways through which they induce these changes. Lastly, we discuss promising avenues for future research investigating the roles of these pathological conditions on retinal metabolism, potentially offering novel therapeutic approaches to combat age-related retinal disease.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101306"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular component transfer between photoreceptor cells of the retina","authors":"Joyce Wang ,&nbsp;Patrick O. Nnoromele ,&nbsp;Ying V. Liu ,&nbsp;Robert J. Johnston Jr. ,&nbsp;Mandeep S. Singh","doi":"10.1016/j.preteyeres.2024.101317","DOIUrl":"10.1016/j.preteyeres.2024.101317","url":null,"abstract":"<div><div>Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as “cell replacement” in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections. The discovery of CCT in the transplantation context triggered a re-interpretation of prior transplantation studies that generally did not include specific CCT assays and thereby broadly emphasized the cell replacement model, reflecting the prevailing understanding of retinal transplantation biology at that time. In addition to clarifying our understanding of photoreceptor biology, CCT has raised the possibility of developing treatments to replenish molecular deficiencies in diseased photoreceptor cells. As the CCT field evolves, investigators have used diverse terminology, and implemented different CCT assays following transplantation in animal models. The non-standardized terminology of CCT and absent minimal assay standards for detection can hinder communication between investigators and comparison between studies. In this review, we discuss the current understanding of CCT, provide an overview of transplantation and regeneration studies in small and large animals, and propose terminology and a minimal assay standard for CCT. Further research on CCT may eventually provide new avenues to treat a range of hereditary and acquired retinopathies while illuminating mechanisms of cell-cell interaction in the retina.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101317"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648143","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":"Corneal cross-linking","authors":"Farhad Hafezi ,&nbsp;Sabine Kling ,&nbsp;Nikki L. Hafezi ,&nbsp;M. Enes Aydemir ,&nbsp;Nan-Ji Lu ,&nbsp;Mark Hillen ,&nbsp;Boris Knyazer ,&nbsp;Shady Awwad ,&nbsp;Cosimo Mazzotta ,&nbsp;Léonard Kollros ,&nbsp;Emilio A. Torres-Netto","doi":"10.1016/j.preteyeres.2024.101322","DOIUrl":"10.1016/j.preteyeres.2024.101322","url":null,"abstract":"<div><div>First introduced over 20 years ago as a treatment for progressive keratoconus, the original “Dresden” corneal cross-linking (CXL) protocol involved riboflavin saturation of the stroma, followed by 30 min of 3 mW/cm²-intensity ultraviolet-A (UV-A) irradiation. This procedure generates reactive oxygen species (ROS) that cross-link stromal molecules, thereby stiffening the cornea and counteracting the ectasia-induced weakening. Due to their large size, riboflavin molecules cannot readily pass through the corneal epithelial cell tight junctions; thus, epithelial debridement was performed. Moreover, the Dresden protocol necessitates a minimal corneal thickness of 400 μm to protect the endothelium from UV-induced damage. While the Dresden protocol is highly effective at enhancing corneal biomechanical strength, there was a strong desire for CXL procedures that would deliver Dresden-like strengthening in a shorter time, in corneas thinner than 400 μm, and without requiring epithelial debridement.</div><div>This review explores the advancements and scientific discoveries that have enabled such improvements. Accelerated CXL protocols, utilizing our increased knowledge about the role of oxygen and photochemical reactions in the cornea have shortened and simplified the procedure duration while maintaining efficacy and safety, improving clinical workflow and patient compliance.</div><div>CXL is not confined to improving biomechanics in corneal ectasia, but rather represents a technique that modulates corneal physiology and biochemistry on multiple levels. Accordingly, CXL indications have expanded to include treating other corneal ectasias, corneal neovascularization, corneal sterile melting, inflammatory dry eye and importantly, infectious keratitis in a procedure termed photoactivated chromophore for keratitis-CXL (PACK-CXL). In PACK-CXL, ROS have a direct pathogen-killing effect, and cross-linking enhances the cornea's resistance to pathogen-produced protease digestion through steric hindrance.</div><div>The distinct requirements of PACK-CXL compared to ectasia treatment have led to the development of different CXL protocols, including higher UV fluences and other chromophore/light combinations, specifically rose bengal and green light. Additionally, combining CXL with vision-enhancing procedures like individualized wavefront- or topographically-guided excimer ablation can regularize a biomechanically stable cornea, improve visual acuity, and potentially eliminate the need for corneal transplantation, leading to long-term improvements in quality of life.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101322"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838404","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":"pH in the vertebrate retina and its naturally occurring and pathological changes","authors":"Andrey V. Dmitriev ,&nbsp;Robert A. Linsenmeier","doi":"10.1016/j.preteyeres.2024.101321","DOIUrl":"10.1016/j.preteyeres.2024.101321","url":null,"abstract":"<div><div>This review summarizes the existing information on the concentration of H⁺ (pH) in vertebrate retinae and its changes due to various reasons. Special features of H⁺ homeostasis that make it different from other ions will be discussed, particularly metabolic production of H⁺ and buffering. The transretinal distribution of extracellular H⁺ concentration ([H⁺]_o) and its changes under illumination and other conditions will be described in detail, since [H⁺]_o is more intensively investigated than intracellular pH. In vertebrate retinae, the highest [H⁺]_o occurs in the inner part of the outer nuclear layer, and decreases toward the RPE, reaching the blood level on the apical side of the RPE. [H⁺]_o falls toward the vitreous as well, but less, so that the inner retina is acidic to the vitreous. Light leads to complex changes with both electrogenic and metabolic origins, culminating in alkalinization. There is a rhythm of [H⁺]_o with H⁺ being higher during circadian night. Extracellular pH can potentially be used as a signal in intercellular volume transmission, but evidence is against pH as a normal controller of fluid transport across the RPE or as a horizontal cell feedback signal. Pathological and experimentally created conditions (systemic metabolic acidosis, hypoxia and ischemia, vascular occlusion, excess glucose and diabetes, genetic disorders, and blockade of carbonic anhydrase) disturb H⁺ homeostasis, mostly producing retinal acidosis, with consequences for retinal blood flow, metabolism and function.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101321"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751203","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":"Standard automated perimetry for glaucoma and diseases of the retina and visual pathways: Current and future perspectives","authors":"Jack Phu ,&nbsp;Sieu K. Khuu ,&nbsp;Lisa Nivison-Smith ,&nbsp;Michael Kalloniatis","doi":"10.1016/j.preteyeres.2024.101307","DOIUrl":"10.1016/j.preteyeres.2024.101307","url":null,"abstract":"<div><div>Static automated perimetry (SAP) remains a mainstay of functional assessment of the visual field in diseases of the visual pathway, such as glaucoma and age-related macular degeneration. The fundamental psychophysical task of responding to stimuli of different levels of contrast has remained minimally changed since its inception in the 1980s, and this is potentially the root of several unresolved issues involving the technique. Enduring issues include the optimisation of SAP parameters for maximising defect detection, the influence of subjective behaviour on the response, structure-function discordance, and ageing- and disease-related changes of the visual pathway. Addressing these issues has been a focus of our research program and is the subject of this manuscript. We will review some of the basic psychophysical principles and methods that have contributed to the development of SAP and their contributions to its output measurements. Parameters that are interrogated include stimulus size and background luminance and their modification to improve defect defection in glaucoma and age-related macular degeneration. We propose frameworks for optimising testing parameters and leveraging the results for changing clinical care. In our pursuit of optimising the structure-function relationship in the eye, several areas of research have been developed and explored, including: the reconciliation of subjective responses in perimetry; by minimising sources of biases, such as Method of Limits we have been able to equate static and kinetic perimetry outputs in relation to underlying structural loci. This also formed the basis for our clustering framework, which groups together statistically similar structural and functional test locations to maximise structure-function concordance. Throughout the manuscript, we review the scientific underpinnings of clinical measurements, framing application into real-world patients to improve clinical practice.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101307"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual inheritance patterns: A spectrum of non-syndromic inherited retinal disease phenotypes with varying molecular mechanisms","authors":"Lara K. Holtes,&nbsp;Suzanne E. de Bruijn,&nbsp;Frans P.M. Cremers,&nbsp;Susanne Roosing","doi":"10.1016/j.preteyeres.2024.101308","DOIUrl":"10.1016/j.preteyeres.2024.101308","url":null,"abstract":"<div><div>Inherited retinal diseases (IRDs) encompass a variety of disease phenotypes and are known to display both clinical and genetic heterogeneity. A further complexity is that for several IRD-associated genes, pathogenic variants have been reported to cause either autosomal dominant (AD) or autosomal recessive (AR) diseases. The possibility of dual inheritance can create a challenge for variant interpretation as well as the genetic counselling of patients. This review aims to determine whether the molecular mechanisms behind the dual inheritance of each IRD-associated gene is well established, not yet properly understood, or if the association is questionable. Each gene is discussed individually in detail due to different protein structures and functions, but there are overlapping characteristics. For example, eight genes only have a limited number of reported pathogenic variants or a hotspot region implicated in the second inheritance pattern. Whereas <em>CRX</em> and <em>RP1</em> display distinct spatial patterns for AR and AD pathogenic variants based on the variant type and/or location. The genes with a questionable dual inheritance, namely <em>AIPL1</em>, <em>CRB1,</em> and <em>RCBTB1</em> highlight the importance of carefully considering allele frequency data. Finally, the crucial role relevant functional studies in animal and cell models play in validating a variant's biochemical or molecular effect is emphasised.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101308"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of epigenetics in corneal health and disease","authors":"Swati Sood ,&nbsp;Anil Tiwari ,&nbsp;Jyoti Sangwan ,&nbsp;Mehak Vohra ,&nbsp;Nishant R. Sinha ,&nbsp;Ratnakar Tripathi ,&nbsp;Virender S. Sangwan ,&nbsp;Rajiv R. Mohan","doi":"10.1016/j.preteyeres.2024.101318","DOIUrl":"10.1016/j.preteyeres.2024.101318","url":null,"abstract":"<div><div>Epigenetics plays a vital role in corneal health and diseases. Epigenetic changes regulate the expression of genes by altering the accessibility of chromatin <em>via</em> histone modifications, DNA methylation and miRNAs without altering DNA sequence. Ocular trauma and infections are common causes of corneal damage, vision impairment, and mono/bilateral blindness worldwide. Mounting literature shows that epigenetic modifications can modulate corneal clarity, function, and pathogenesis including inflammation, wound healing, fibrosis, and neovascularization. Additionally, epigenetic modifications can be targeted to reverse corneal pathologies and develop interventional therapies. However, current understanding on how epigenetic modifications lead to corneal abnormalities and diseases is limited. This review provides in-depth knowledge and mechanistic understanding of epigenetics alterations in corneal pathogenesis, and information on potential epigenetic targets for treatment of corneal diseases.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101318"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639694","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":"Multiple gene therapy as a tool for regulating the expression of molecules involved in neovascular age-related macular degeneration","authors":"Thomas J. Corydon ,&nbsp;Toke Bek","doi":"10.1016/j.preteyeres.2024.101323","DOIUrl":"10.1016/j.preteyeres.2024.101323","url":null,"abstract":"<div><div>Anti-vascular endothelial growth factor (VEGF) therapies have revolutionized the treatment of neovascular age-related macular degeneration (nAMD) and other retinal diseases. However, the necessity for repeated intravitreal injections and the observation of variable treatment responses calls for new treatment modalities where fewer and more effective interventions can result in a clinical effect. Gene therapy might be such an alternative, and therefore the development and clinical application of gene therapy aimed at modifying gene expression has received considerable attention. The article reviews current knowledge of the background, pathophysiological mechanisms, technologies, limitations, and future directions for gene therapy aimed at modifying the synthesis of compounds involved in acquired and senescent retinal disease.</div><div>The authors have contributed to the field by developing gene therapy to reduce the expression of vascular endothelial growth factor (VEGF), as well as multiple gene therapy for simultaneous downregulation of the synthesis of VEGF and upregulation of pigment epithelium-derived factor (PEDF) using adeno-associated virus (AAV) vectors. It is suggested that such multi-target gene therapy might be included in future treatments of retinal diseases where the underlying mechanisms are complex and cannot be attributed to one specific mediator. Such diseases might include dry AMD (dAMD) with geographic atrophy, but also diabetic macular edema (DME) and retinal vein occlusion (RVO). Gene therapy can be expected to be most beneficial for the patients in need of multiple intra-vitreal injections and in whom the therapeutic response is insufficient. It is concluded, that in parallel with basic research, there is a need for clinical studies aimed at identifying factors that can be used to identify patients who will benefit from gene therapy already at the time of diagnosis of the retinal disease.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101323"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Optical coherence tomography in the management of diabetic macular oedema” [Prog. Retin. Eye Res. 98 (2024) 101220]","authors":"Simon KH. Szeto ,&nbsp;Timothy YY. Lai ,&nbsp;Stela Vujosevic ,&nbsp;Jennifer K. Suns ,&nbsp;SriniVas R. Sadda ,&nbsp;Gavin Tan ,&nbsp;Sobha Sivaprasad ,&nbsp;Tien Y. Wong ,&nbsp;Carol Y. Cheung","doi":"10.1016/j.preteyeres.2024.101319","DOIUrl":"10.1016/j.preteyeres.2024.101319","url":null,"abstract":"","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"104 ","pages":"Article 101319"},"PeriodicalIF":18.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771861","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":"Pathobiology of the crystalline lens in Stickler syndrome","authors":"Martin P. Snead ,&nbsp;Frank J. Lovicu ,&nbsp;Thomas RW. Nixon ,&nbsp;Allan J. Richards ,&nbsp;Howard Martin","doi":"10.1016/j.preteyeres.2024.101304","DOIUrl":"10.1016/j.preteyeres.2024.101304","url":null,"abstract":"<div><h3>Purpose</h3><div>The Stickler syndromes are a group of connective tissue disorders characterised by congenital myopia, giant retinal tear and retinal detachment, cleft palate, hearing loss and premature arthropathy. Patients with Stickler syndrome are also susceptible to abnormalities of the crystalline lens. Since neither type II or type XI collagen (those typically affected in the vast majority of Stickler patients) are highly expressed in the lens, this observational cohort study explores potential alternative mechanisms to explain why patients frequently exhibit such unusual but characteristic types of cataract.</div></div><div><h3>Methods</h3><div>Author observations drawn from a cohort of over 1800 patients with genetically confirmed Stickler syndrome.</div></div><div><h3>Results</h3><div>3 distinct lens pathologies were identified. Firstly, a congenital quadrantic lamellar opacity. This can be present in both type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome. Secondly, early onset Pantone 557 C blue-green nuclear cataract. Thirdly, congenital lens coloboma associated with localised zonule deficiency.</div></div><div><h3>Conclusions</h3><div>The characteristic quadrantic lamellar lens opacity can be helpful in alerting to the possible diagnosis, particularly in sub-groups with an ocular-only phenotype.</div><div>Temporal and spatial signalling pathways shared embryologically by both the developing vitreous body and crystalline lens suggest an ancillary role of the fibrillar collagens in cell signalling beyond their basic structural function. A common pathway of TGFβ/BMP super-family dysregulation may be shared with allied disorders associated with both retinal detachment and cataract as well as the pathobiology linking retinal detachment and cataract in the population at large.</div><div>Congenital lens coloboma associated with localised zonule deficiency can increase the difficulty and risks of cataract surgery. Strategies to mitigate such risks are presented.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101304"},"PeriodicalIF":18.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}