Progress in Retinal and Eye Research最新文献

{"title":"Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments","authors":"Ghazi O. Bou Ghanem,&nbsp;Lauren K. Wareham,&nbsp;David J. Calkins","doi":"10.1016/j.preteyeres.2024.101261","DOIUrl":"10.1016/j.preteyeres.2024.101261","url":null,"abstract":"<div><p>Glaucoma is the leading cause of irreversible blindness globally. The disease causes vision loss due to neurodegeneration of the retinal ganglion cell (RGC) projection to the brain through the optic nerve. Glaucoma is associated with sensitivity to intraocular pressure (IOP). Thus, mainstay treatments seek to manage IOP, though many patients continue to lose vision. To address neurodegeneration directly, numerous preclinical studies seek to develop protective or reparative therapies that act independently of IOP. These include growth factors, compounds targeting metabolism, anti-inflammatory and antioxidant agents, and neuromodulators. Despite success in experimental models, many of these approaches fail to translate into clinical benefits. Several factors contribute to this challenge. Firstly, the anatomic structure of the optic nerve head differs between rodents, nonhuman primates, and humans. Additionally, animal models do not replicate the complex glaucoma pathophysiology in humans. Therefore, to enhance the success of translating these findings, we propose two approaches. First, thorough evaluation of experimental targets in multiple animal models, including nonhuman primates, should precede clinical trials. Second, we advocate for combination therapy, which involves using multiple agents simultaneously, especially in the early and potentially reversible stages of the disease. These strategies aim to increase the chances of successful neuroprotective treatment for glaucoma.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101261"},"PeriodicalIF":17.8,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288866","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":"Glycative stress as a cause of macular degeneration","authors":"Eloy Bejarano ,&nbsp;Alicia Domenech-Bendaña ,&nbsp;Norma Avila-Portillo ,&nbsp;Sheldon Rowan ,&nbsp;Sachini Edirisinghe ,&nbsp;Allen Taylor","doi":"10.1016/j.preteyeres.2024.101260","DOIUrl":"10.1016/j.preteyeres.2024.101260","url":null,"abstract":"<div><p>People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health<em>.</em> The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes<em>.</em> In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using <em>in vitro</em> and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101260"},"PeriodicalIF":17.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194485","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":"How gut microbiota may impact ocular surface homeostasis and related disorders","authors":"Marc Labetoulle ,&nbsp;Christophe Baudouin ,&nbsp;Jose M. Benitez del Castillo ,&nbsp;Maurizio Rolando ,&nbsp;Maria Rescigno ,&nbsp;Elisabeth M. Messmer ,&nbsp;Pasquale Aragona","doi":"10.1016/j.preteyeres.2024.101250","DOIUrl":"10.1016/j.preteyeres.2024.101250","url":null,"abstract":"<div><p>Changes in the bacterial flora in the gut, also described as gut microbiota, are readily acknowledged to be associated with several systemic diseases, especially those with an inflammatory, neuronal, psychological or hormonal factor involved in the pathogenesis and/or the perception of the disease. Maintaining ocular surface homeostasis is also based on all these four factors, and there is accumulating evidence in the literature on the relationship between gut microbiota and ocular surface diseases. The mechanisms involved are mostly interconnected due to the interaction of central and peripheral neuronal networks, inflammatory effectors and the hormonal system. A better understanding of the influence of the gut microbiota on the maintenance of ocular surface homeostasis, and on the onset or persistence of ocular surface disorders could bring new insights and help elucidate the epidemiology and pathology of ocular surface dynamics in health and disease. Revealing the exact nature of these associations could be of paramount importance for developing a holistic approach using highly promising new therapeutic strategies targeting ocular surface diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101250"},"PeriodicalIF":17.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000156/pdfft?md5=b67c068d00faa8fa767a90eb51da509c&pid=1-s2.0-S1350946224000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068669","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":"Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases","authors":"Mandy Hector ,&nbsp;Thomas Langmann ,&nbsp;Anne Wolf","doi":"10.1016/j.preteyeres.2024.101249","DOIUrl":"10.1016/j.preteyeres.2024.101249","url":null,"abstract":"<div><p>Translocator protein (18 kDa) (Tspo), formerly known as peripheral benzodiazepine receptor is a highly conserved transmembrane protein primarily located in the outer mitochondrial membrane. In the central nervous system (CNS), especially in glia cells, Tspo is upregulated upon inflammation. Consequently, Tspo was used as a tool for diagnostic <em>in vivo</em> imaging of neuroinflammation in the brain and as a potential therapeutic target. Several synthetic Tspo ligands have been explored as immunomodulatory and neuroprotective therapy approaches. Although the function of Tspo and how its ligands exert these beneficial effects is not fully clear, it became a research topic of interest, especially in ocular diseases in the past few years. This review summarizes state-of-the-art knowledge of Tspo expression and its proposed functions in different cells of the retina including microglia, retinal pigment epithelium and Müller cells. Tspo is involved in cytokine signaling, oxidative stress and reactive oxygen species production, calcium signaling, neurosteroid synthesis, energy metabolism, and cholesterol efflux. We also highlight recent developments in preclinical models targeting Tspo and summarize the relevance of Tspo biology for ocular and retinal diseases. We conclude that glial upregulation of Tspo in different ocular pathologies and the use of Tspo ligands as promising therapeutic approaches in preclinical studies underline the importance of Tspo as a potential disease-modifying protein.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101249"},"PeriodicalIF":17.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023947","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":"Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity","authors":"Marzena Kurzawa-Akanbi ,&nbsp;Nikolaos Tzoumas ,&nbsp;Julio C. Corral-Serrano ,&nbsp;Rosellina Guarascio ,&nbsp;David H. Steel ,&nbsp;Michael E. Cheetham ,&nbsp;Lyle Armstrong ,&nbsp;Majlinda Lako","doi":"10.1016/j.preteyeres.2024.101248","DOIUrl":"10.1016/j.preteyeres.2024.101248","url":null,"abstract":"<div><p>Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding retinal diseases is therefore key to advance effective treatments, requiring <em>in vitro</em> models replicating pathology and allowing quantitative assessments for drug discovery. Pluripotent stem cells (PSCs) provide a unique solution given their limitless supply and ability to differentiate into light-responsive retinal tissues encompassing all cell types. This review focuses on the history and current state of photoreceptor and retinal pigment epithelium (RPE) cell generation from PSCs. We explore the applications of this technology in disease modelling, experimental therapy testing, biomarker identification, and toxicity studies. We consider challenges in scalability, standardisation, and reproducibility, and stress the importance of incorporating vasculature and immune cells into retinal organoids. We advocate for high-throughput automation in data acquisition and analyses and underscore the value of advanced micro-physiological systems that fully capture the interactions between the neural retina, RPE, and choriocapillaris.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101248"},"PeriodicalIF":17.8,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000132/pdfft?md5=bcd3eac64c7f370b88be13ead82062f1&pid=1-s2.0-S1350946224000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773988","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":"Modeling complex age-related eye disease","authors":"Silke Becker ,&nbsp;Zia L'Ecuyer ,&nbsp;Bryan W. Jones ,&nbsp;Moussa A. Zouache ,&nbsp;Fiona S. McDonnell ,&nbsp;Frans Vinberg","doi":"10.1016/j.preteyeres.2024.101247","DOIUrl":"10.1016/j.preteyeres.2024.101247","url":null,"abstract":"<div><p>Modeling complex eye diseases like age-related macular degeneration (AMD) and glaucoma poses significant challenges, since these conditions depend highly on age-related changes that occur over several decades, with many contributing factors remaining unknown. Although both diseases exhibit a relatively high heritability of &gt;50%, a large proportion of individuals carrying AMD- or glaucoma-associated genetic risk variants will never develop these diseases. Furthermore, several environmental and lifestyle factors contribute to and modulate the pathogenesis and progression of AMD and glaucoma.</p><p>Several strategies replicate the impact of genetic risk variants, pathobiological pathways and environmental and lifestyle factors in AMD and glaucoma in mice and other species. In this review we will primarily discuss the most commonly available mouse models, which have and will likely continue to improve our understanding of the pathobiology of age-related eye diseases. Uncertainties persist whether small animal models can truly recapitulate disease progression and vision loss in patients, raising doubts regarding their usefulness when testing novel gene or drug therapies. We will elaborate on concerns that relate to shorter lifespan, body size and allometries, lack of macula and a true lamina cribrosa, as well as absence and sequence disparities of certain genes and differences in their chromosomal location in mice.</p><p>Since biological, rather than chronological, age likely predisposes an organism for both glaucoma and AMD, more rapidly aging organisms like small rodents may open up possibilities that will make research of these diseases more timely and financially feasible. On the other hand, due to the above-mentioned anatomical and physiological features, as well as pharmacokinetic and -dynamic differences small animal models are not ideal to study the natural progression of vision loss or the efficacy and safety of novel therapies. In this context, we will also discuss the advantages and pitfalls of alternative models that include larger species, such as non-human primates and rabbits, patient-derived retinal organoids, and human organ donor eyes.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101247"},"PeriodicalIF":17.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139747324","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":"Central serous chorioretinopathy: An evidence-based treatment guideline","authors":"Helena M.A. Feenstra ,&nbsp;Elon H.C. van Dijk ,&nbsp;Chui Ming Gemmy Cheung ,&nbsp;Kyoko Ohno-Matsui ,&nbsp;Timothy Y.Y. Lai ,&nbsp;Hideki Koizumi ,&nbsp;Michael Larsen ,&nbsp;Giuseppe Querques ,&nbsp;Susan M. Downes ,&nbsp;Suzanne Yzer ,&nbsp;Mark P. Breazzano ,&nbsp;Yousif Subhi ,&nbsp;Ramin Tadayoni ,&nbsp;Siegfried G. Priglinger ,&nbsp;Laurenz J.B. Pauleikhoff ,&nbsp;Clemens A.K. Lange ,&nbsp;Anat Loewenstein ,&nbsp;Roselie M.H. Diederen ,&nbsp;Reinier O. Schlingemann ,&nbsp;Carel B. Hoyng ,&nbsp;Camiel J.F. Boon","doi":"10.1016/j.preteyeres.2024.101236","DOIUrl":"10.1016/j.preteyeres.2024.101236","url":null,"abstract":"<div><p>Central serous chorioretinopathy (CSC) is a relatively common disease that causes vision loss due to macular subretinal fluid leakage and it is often associated with reduced vision-related quality of life. In CSC, the leakage of subretinal fluid through defects in the retinal pigment epithelial layer's outer blood-retina barrier appears to occur secondary to choroidal abnormalities and dysfunction. The treatment of CSC is currently the subject of controversy, although recent data obtained from several large randomized controlled trials provide a wealth of new information that can be used to establish a treatment algorithm. Here, we provide a comprehensive overview of our current understanding regarding the pathogenesis of CSC, current therapeutic strategies, and an evidence-based treatment guideline for CSC. In acute CSC, treatment can often be deferred for up to 3–4 months after diagnosis; however, early treatment with either half-dose or half-fluence photodynamic therapy (PDT) with the photosensitive dye verteporfin may be beneficial in selected cases. In chronic CSC, half-dose or half-fluence PDT, which targets the abnormal choroid, should be considered the preferred treatment. If PDT is unavailable, chronic CSC with focal, non-central leakage on angiography may be treated using conventional laser photocoagulation. CSC with concurrent macular neovascularization should be treated with half-dose/half-fluence PDT and/or intravitreal injections of an anti-vascular endothelial growth factor compound. Given the current shortage of verteporfin and the paucity of evidence supporting the efficacy of other treatment options, future studies—ideally, well-designed randomized controlled trials—are needed in order to evaluate new treatment options for CSC.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101236"},"PeriodicalIF":17.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000016/pdfft?md5=ad36b9e0851c96c3a0f3082dbeed1d93&pid=1-s2.0-S1350946224000016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659639","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":"Phenotyping and genotyping inherited retinal diseases: Molecular genetics, clinical and imaging features, and therapeutics of macular dystrophies, cone and cone-rod dystrophies, rod-cone dystrophies, Leber congenital amaurosis, and cone dysfunction syndromes","authors":"Michalis Georgiou ,&nbsp;Anthony G. Robson ,&nbsp;Kaoru Fujinami ,&nbsp;Thales A.C. de Guimarães ,&nbsp;Yu Fujinami-Yokokawa ,&nbsp;Malena Daich Varela ,&nbsp;Nikolas Pontikos ,&nbsp;Angelos Kalitzeos ,&nbsp;Omar A. Mahroo ,&nbsp;Andrew R. Webster ,&nbsp;Michel Michaelides","doi":"10.1016/j.preteyeres.2024.101244","DOIUrl":"10.1016/j.preteyeres.2024.101244","url":null,"abstract":"<div><p>Inherited retinal diseases (IRD) are a leading cause of blindness in the working age population and in children. The scope of this review is to familiarise clinicians and scientists with the current landscape of molecular genetics, clinical phenotype, retinal imaging and therapeutic prospects/completed trials in IRD. Herein we present in a comprehensive and concise manner: (i) macular dystrophies (Stargardt disease (<em>ABCA4</em>), X-linked retinoschisis (<em>RS1</em>), Best disease (<em>BEST1</em>), <em>PRPH2-</em>associated pattern dystrophy, Sorsby fundus dystrophy (<em>TIMP3</em>), and autosomal dominant drusen (<em>EFEMP1</em>)), (ii) cone and cone-rod dystrophies (<em>GUCA1A</em>, <em>PRPH2</em>, <em>ABCA4, KCNV2</em> and <em>RPGR</em>)<em>,</em> (iii) predominant rod or rod-cone dystrophies (retinitis pigmentosa, enhanced S-Cone syndrome (<em>NR2E3</em>), Bietti crystalline corneoretinal dystrophy (<em>CYP4V2</em>)), (iv) Leber congenital amaurosis/early-onset severe retinal dystrophy (<em>GUCY2D</em>, <em>CEP290</em>, <em>CRB1</em>, <em>RDH12</em>, <em>RPE65, TULP1</em>, <em>AIPL1</em> and <em>NMNAT1</em>)<em>,</em> (v) cone dysfunction syndromes (achromatopsia (<em>CNGA3, CNGB3, PDE6C, PDE6H, GNAT2, ATF6</em>), X-linked cone dysfunction with myopia and dichromacy (Bornholm Eye disease; <em>OPN1LW/OPN1MW</em> array), oligocone trichromacy, and blue-cone monochromatism (<em>OPN1LW/OPN1MW</em> array)). Whilst we use the aforementioned classical phenotypic groupings, a key feature of IRD is that it is characterised by tremendous heterogeneity and variable expressivity, with several of the above genes associated with a range of phenotypes.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101244"},"PeriodicalIF":17.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139550598","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":"Optic neuropathy in high myopia: Glaucoma or high myopia or both?","authors":"Xiulan Zhang ,&nbsp;Jingwen Jiang ,&nbsp;Kangjie Kong ,&nbsp;Fei Li ,&nbsp;Shida Chen ,&nbsp;Peiyuan Wang ,&nbsp;Yunhe Song ,&nbsp;Fengbin Lin ,&nbsp;Timothy P.H. Lin ,&nbsp;Linda M. Zangwill ,&nbsp;Kyoko Ohno-Matsui ,&nbsp;Jost B. Jonas ,&nbsp;Robert N. Weinreb ,&nbsp;Dennis S.C. Lam ,&nbsp;Glaucoma Suspects with High Myopia Study Group","doi":"10.1016/j.preteyeres.2024.101246","DOIUrl":"10.1016/j.preteyeres.2024.101246","url":null,"abstract":"<div><p>Due to the increasing prevalence of high myopia<span><span><span> around the world, structural and functional damages to the optic nerve in high myopia has recently attracted much attention. Evidence has shown that high myopia is related to the development of glaucomatous or glaucoma-like optic neuropathy<span>, and that both have many common features. These similarities often pose a diagnostic challenge that will affect the future management of glaucoma suspects in high myopia. In this review, we summarize similarities and differences in optic neuropathy arising from non-pathologic high myopia and glaucoma by considering their respective structural and functional characteristics on fundus photography, </span></span>optical coherence tomography scanning, and </span>visual field tests. These features may also help to distinguish the underlying mechanisms of the optic neuropathies and to determine management strategies for patients with high myopia and glaucoma.</span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"99 ","pages":"Article 101246"},"PeriodicalIF":17.8,"publicationDate":"2024-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139505821","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":"Mechanisms of blood-retinal barrier disruption related to intraocular inflammation and malignancy","authors":"Oren Tomkins-Netzer ,&nbsp;Rachael Niederer ,&nbsp;John Greenwood ,&nbsp;Ido Didi Fabian ,&nbsp;Yonatan Serlin ,&nbsp;Alon Friedman ,&nbsp;Sue Lightman","doi":"10.1016/j.preteyeres.2024.101245","DOIUrl":"10.1016/j.preteyeres.2024.101245","url":null,"abstract":"<div><p><span><span><span>Blood-retinal barrier (BRB) disruption is a common accompaniment of intermediate, posterior and panuveitis<span> causing leakage into the retina and macular oedema resulting in </span></span>vision loss<span>. It is much less common in anterior uveitis or </span></span>in patients<span> with intraocular lymphoma who may have marked signs of intraocular inflammation. New </span></span>drugs<span> used for chemotherapy (cytarabine, immune checkpoint inhibitors<span>, BRAF inhibitors, EGFR inhibitors<span>, bispecific anti-EGFR inhibitors, MET receptor<span> inhibitors and Bruton tyrosine kinase inhibitors) can also cause different types of uveitis and BRB disruption. As malignant disease itself can cause uveitis, particularly from breast, lung and gastrointestinal tract cancers, it can be clinically difficult to sort out the cause of BRB disruption. Immunosuppression due to malignant disease and/or chemotherapy can lead to infection which can also cause BRB disruption and intraocular infection.</span></span></span></span></p><p><span>In this paper we address the pathophysiology of BRB disruption related to intraocular inflammation and </span>malignancy, methods for estimating the extent and effect of the disruption and examine why some types of intraocular inflammation and malignancy cause BRB disruption and others do not. Understanding this may help sort and manage these patients, as well as devise future therapeutic approaches.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"99 ","pages":"Article 101245"},"PeriodicalIF":17.8,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139489755","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}