Progress in Retinal and Eye Research最新文献

{"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":"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":"Syndromic retinitis pigmentosa","authors":"Jessica S. Karuntu ,&nbsp;Hind Almushattat ,&nbsp;Xuan-Thanh-An Nguyen ,&nbsp;Astrid S. Plomp ,&nbsp;Ronald J.A. Wanders ,&nbsp;Carel B. Hoyng ,&nbsp;Mary J. van Schooneveld ,&nbsp;Nicoline E. Schalij-Delfos ,&nbsp;Marion M. Brands ,&nbsp;Bart P. Leroy ,&nbsp;Clara D.M. van Karnebeek ,&nbsp;Arthur A. Bergen ,&nbsp;Maria M. van Genderen ,&nbsp;Camiel J.F. Boon","doi":"10.1016/j.preteyeres.2024.101324","DOIUrl":"10.1016/j.preteyeres.2024.101324","url":null,"abstract":"<div><div>Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20–30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives. Given the diverse clinical and genetic landscape of syndromic RP, the diagnosis may be challenging. However, an accurate and timely diagnosis is essential for optimal clinical management, prognostication, and potential treatment. Broadly, the syndromes associated with RP can be categorized into ciliopathies, inherited metabolic disorders, mitochondrial disorders, and miscellaneous syndromes. Among the ciliopathies associated with RP, Usher syndrome and Bardet-Biedl syndrome are the most well-known. Less common ciliopathies include Cohen syndrome, Joubert syndrome, cranioectodermal dysplasia, asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, and RHYNS syndrome.</div><div>Several inherited metabolic disorders can present with RP, including Zellweger spectrum disorders, adult Refsum disease, α-methylacyl-CoA racemase deficiency, certain mucopolysaccharidoses, ataxia with vitamin E deficiency, abetalipoproteinemia, several neuronal ceroid lipofuscinoses, mevalonic aciduria, PKAN/HARP syndrome, PHARC syndrome, and methylmalonic acidaemia with homocystinuria type cobalamin (cbl) C disease.</div><div>Due to the mitochondria's essential role in supplying continuous energy to the retina, disruption of mitochondrial function can lead to RP, as seen in Kearns-Sayre syndrome, NARP syndrome, primary coenzyme Q10 deficiency, <em>SSBP1</em>-associated disease, and long chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Lastly, Cockayne syndrome and PERCHING syndrome can present with RP, but they do not fit the abovementioned hierarchy and are thus categorized as miscellaneous.</div><div>Several first-in-human clinical trials are underway or in preparation for some of these syndromic forms of RP.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"107 ","pages":"Article 101324"},"PeriodicalIF":18.6,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903530","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":"Unraveling ptosis: A comprehensive review of clinical manifestations, genetics, and treatment","authors":"Hao Deng ,&nbsp;Qianling Zhang ,&nbsp;Junhui Yi ,&nbsp;Lamei Yuan","doi":"10.1016/j.preteyeres.2024.101327","DOIUrl":"10.1016/j.preteyeres.2024.101327","url":null,"abstract":"<div><div>Ptosis is defined as an abnormally low-lying upper eyelid margin on the primary gaze, generally resulting from a congenital or acquired abnormality of the nerves or muscles that control the eyelid. Ptosis can occur alone or concurrently as an ocular or systemic syndrome, and the prevalence of ptosis varies among different countries and populations. Isolated ptosis typically causes aesthetic problems in patients and can lead to functional ophthalmic problems in severe cases. In individuals with syndromic ptosis, ptosis can be a warning of serious medical problems. There are different approaches to classification, depending on the onset time or the etiology of ptosis, and the clinical characteristics of congenital and acquired ptosis also differ. Pedigree and genetic analysis have demonstrated that hereditary ptosis is clinically heterogeneous, with incomplete concordance and variable expressivity. A number of genetic loci and genes responsible for hereditary isolated and syndromic ptosis have been reported. Optimal surgical timing and proper method are truly critical for avoiding the risk of potentially severe outcomes from ptosis and minimizing surgical complications, which are challenging as the pathogenesis is still indistinct and the anatomy is complex. This review provides a comprehensive review of ptosis, by summarizing the clinical manifestations, classification, diagnosis, genetics, treatment, and prognosis, as well as the bound anatomy of upper eyelid.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101327"},"PeriodicalIF":18.6,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896825","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":"Healing the cornea: Exploring the therapeutic solutions offered by MSCs and MSC-derived EVs","authors":"Manon Jammes ,&nbsp;Abbas Tabasi ,&nbsp;Trung Bach ,&nbsp;Thomas Ritter","doi":"10.1016/j.preteyeres.2024.101325","DOIUrl":"10.1016/j.preteyeres.2024.101325","url":null,"abstract":"<div><div>Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs). Consequently, using MSC-EVs emerged as a pioneering strategy to mitigate the risks related to cell therapy while providing MSC therapeutic benefits. Despite the promises given by MSC- and MSC-EV-based approaches, many improvements are considered to optimize the therapeutic significance of these therapies. This review aspires to provide a comprehensive and detailed overview of current knowledge on corneal therapies involving MSCs and MSC-EVs, the strategies currently under evaluation, and the gaps remaining to be addressed for clinical implementation. From encapsulating MSCs or their EVs into biomaterials to enhance the ocular retention time to loading MSC-EVs with therapeutic drugs, a wide range of ground-breaking strategies are currently contemplated to lead to the safest and most effective treatments. Promising research initiatives also include diverse gene therapies and the targeting of specific cell types through the modification of the EV surface, paving the way for future therapeutic innovations. As one of the most important challenges, MSC-EV large-scale production strategies are extensively investigated and offer a wide array of possibilities to meet the needs of clinical applications.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"105 ","pages":"Article 101325"},"PeriodicalIF":18.6,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872762","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":"2024-11-16","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":"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":"2024-11-14","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":"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":"2024-10-31","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}