Eric E. Gabison , Antoine Rousseau , Marc Labetoulle , Anas Gazzah , Benjamin Besse
{"title":"Ocular adverse events associated with antibody-drug conjugates used in cancer: Focus on pathophysiology and management strategies","authors":"Eric E. Gabison , Antoine Rousseau , Marc Labetoulle , Anas Gazzah , Benjamin Besse","doi":"10.1016/j.preteyeres.2024.101302","DOIUrl":"10.1016/j.preteyeres.2024.101302","url":null,"abstract":"<div><div>Antibody-drug conjugates (ADCs) are designed to maximize cancer cell death with lower cytotoxicity toward noncancerous cells and are an increasingly valuable option for targeted cancer therapies. However, anticancer treatment with ADCs may be associated with ocular adverse events (AEs) such as dry eye, conjunctivitis, photophobia, blurred vision, and corneal abnormalities. While the pathophysiology of ADC-related ocular AEs has not been fully elucidated, most ocular AEs are attributed to off-target effects. Product labelling for approved ADCs includes drug-specific guidance for dose modification and management of ocular AEs; however, limited data are available regarding effective strategies to minimize and mitigate ocular AEs. Overall, the majority of ocular AEs are reversible through dose modification or supportive care. Eye care providers play key roles in monitoring patients receiving ADC therapy for ocular signs and symptoms to allow for the early detection of ADC-related ocular AEs and to ensure the timely administration of appropriate treatment. Therefore, awareness is needed to help ophthalmologists to identify treatment-related ocular AEs and provide effective management in collaboration with oncologists as part of the patient's cancer care team. This review provides an overview of ocular AEs that may occur with approved and investigational ADC anticancer treatments, including potential underlying mechanisms for ADC-related ocular AEs. It also discusses clinical management practices relevant to ophthalmologists for prevention, monitoring, and management of ADC-related ocular AEs. In collaboration with oncologists, ophthalmologists play a vital role in caring for patients with cancer by assisting with the prompt recognition, mitigation, and management of treatment-related ocular AEs.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101302"},"PeriodicalIF":18.6,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294155","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}
Elena K. Schneider-Futschik , Yimin Zhu , Danni Li , Mark D. Habgood , Bao N. Nguyen , Ines Pankonien , Margarida D. Amaral , Laura E. Downie , Holly R. Chinnery
{"title":"The role of CFTR in the eye, and the effect of early highly effective modulator treatment for cystic fibrosis on eye health","authors":"Elena K. Schneider-Futschik , Yimin Zhu , Danni Li , Mark D. Habgood , Bao N. Nguyen , Ines Pankonien , Margarida D. Amaral , Laura E. Downie , Holly R. Chinnery","doi":"10.1016/j.preteyeres.2024.101299","DOIUrl":"10.1016/j.preteyeres.2024.101299","url":null,"abstract":"<div><div>Cystic fibrosis transmembrane conductance regulator (CFTR) is a protein that plays a crucial role in various human organs, including the respiratory and digestive systems. Dysfunctional CFTR is the key variant of the lethal genetic disorder, cystic fibrosis (CF). In the past decade, highly effective CFTR modulator therapies, including elexacaftor-tezacaftor-ivacaftor, have revolutionised CF management by correcting the underlying molecular defect to improve patient outcomes and life expectancy. Despite demonstrating multiorgan efficacy, clinical studies have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of crystalline lens pathologies in young children on CFTR modulators, and in breastfed infants born to individuals who were on CFTR modulator treatment during pregnancy. CFTR is present in multiple tissues during embryonic development, including the eye, and its expression can be influenced by genetic and environmental factors. This review summarises the role of CFTR in the eye, and the potential impact of CFTR on eye function and vision later in life. This information provides a framework for understanding the use and possible effects of CFTR-modulating therapeutics in the context of eye health, including the potential to leverage the eye for non-invasive and accessible diagnostic and monitoring capabilities in patients with CF.</div></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101299"},"PeriodicalIF":18.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154938","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}
Jacqueline Chua , Bingyao Tan , Damon Wong , Gerhard Garhöfer , Xin Wei Liew , Alina Popa-Cherecheanu , Calvin Woon Loong Chin , Dan Milea , Christopher Li-Hsian Chen , Leopold Schmetterer
{"title":"Optical coherence tomography angiography of the retina and choroid in systemic diseases","authors":"Jacqueline Chua , Bingyao Tan , Damon Wong , Gerhard Garhöfer , Xin Wei Liew , Alina Popa-Cherecheanu , Calvin Woon Loong Chin , Dan Milea , Christopher Li-Hsian Chen , Leopold Schmetterer","doi":"10.1016/j.preteyeres.2024.101292","DOIUrl":"10.1016/j.preteyeres.2024.101292","url":null,"abstract":"<div><p>Optical coherence tomography angiography (OCTA) has transformed ocular vascular imaging, revealing microvascular changes linked to various systemic diseases. This review explores its applications in diabetes, hypertension, cardiovascular diseases, and neurodegenerative diseases. While OCTA provides a valuable window into the body's microvasculature, interpreting the findings can be complex. Additionally, challenges exist due to the relative non-specificity of its findings where changes observed in OCTA might not be unique to a specific disease, variations between OCTA machines, the lack of a standardized normative database for comparison, and potential image artifacts. Despite these limitations, OCTA holds immense potential for the future. The review highlights promising advancements like quantitative analysis of OCTA images, integration of artificial intelligence for faster and more accurate interpretation, and multi-modal imaging combining OCTA with other techniques for a more comprehensive characterization of the ocular vasculature. Furthermore, OCTA's potential future role in personalized medicine, enabling tailored treatment plans based on individual OCTA findings, community screening programs for early disease detection, and longitudinal studies tracking disease progression over time is also discussed. In conclusion, OCTA presents a significant opportunity to improve our understanding and management of systemic diseases. Addressing current limitations and pursuing these exciting future directions can solidify OCTA as an indispensable tool for diagnosis, monitoring disease progression, and potentially guiding treatment decisions across various systemic health conditions.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101292"},"PeriodicalIF":18.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000570/pdfft?md5=8bcc70f21512e907c81bbda35249423b&pid=1-s2.0-S1350946224000570-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111471","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}
Fei Li , Deming Wang , Zefeng Yang , Yinhang Zhang , Jiaxuan Jiang , Xiaoyi Liu , Kangjie Kong , Fengqi Zhou , Clement C. Tham , Felipe Medeiros , Ying Han , Andrzej Grzybowski , Linda M. Zangwill , Dennis S.C. Lam , Xiulan Zhang
{"title":"The AI revolution in glaucoma: Bridging challenges with opportunities","authors":"Fei Li , Deming Wang , Zefeng Yang , Yinhang Zhang , Jiaxuan Jiang , Xiaoyi Liu , Kangjie Kong , Fengqi Zhou , Clement C. Tham , Felipe Medeiros , Ying Han , Andrzej Grzybowski , Linda M. Zangwill , Dennis S.C. Lam , Xiulan Zhang","doi":"10.1016/j.preteyeres.2024.101291","DOIUrl":"10.1016/j.preteyeres.2024.101291","url":null,"abstract":"<div><p>Recent advancements in artificial intelligence (AI) herald transformative potentials for reshaping glaucoma clinical management, improving screening efficacy, sharpening diagnosis precision, and refining the detection of disease progression. However, incorporating AI into healthcare usages faces significant hurdles in terms of developing algorithms and putting them into practice. When creating algorithms, issues arise due to the intensive effort required to label data, inconsistent diagnostic standards, and a lack of thorough testing, which often limits the algorithms' widespread applicability. Additionally, the “black box” nature of AI algorithms may cause doctors to be wary or skeptical. When it comes to using these tools, challenges include dealing with lower-quality images in real situations and the systems' limited ability to work well with diverse ethnic groups and different diagnostic equipment. Looking ahead, new developments aim to protect data privacy through federated learning paradigms, improving algorithm generalizability by diversifying input data modalities, and augmenting datasets with synthetic imagery. The integration of smartphones appears promising for using AI algorithms in both clinical and non-clinical settings. Furthermore, bringing in large language models (LLMs) to act as interactive tool in medicine may signify a significant change in how healthcare will be delivered in the future. By navigating through these challenges and leveraging on these as opportunities, the field of glaucoma AI will not only have improved algorithmic accuracy and optimized data integration but also a paradigmatic shift towards enhanced clinical acceptance and a transformative improvement in glaucoma care.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101291"},"PeriodicalIF":18.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073802","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}
Victor T.T. Chan , An Ran Ran , Siegfried K. Wagner , Herbert Y.H. Hui , Xiaoyan Hu , Ho Ko , Sharon Fekrat , Yaxing Wang , Cecilia S. Lee , Alvin L. Young , Clement C. Tham , Yih Chung Tham , Pearse A. Keane , Dan Milea , Christopher Chen , Tien Yin Wong , Vincent C.T. Mok , Carol Y. Cheung
{"title":"Value proposition of retinal imaging in Alzheimer's disease screening: A review of eight evolving trends","authors":"Victor T.T. Chan , An Ran Ran , Siegfried K. Wagner , Herbert Y.H. Hui , Xiaoyan Hu , Ho Ko , Sharon Fekrat , Yaxing Wang , Cecilia S. Lee , Alvin L. Young , Clement C. Tham , Yih Chung Tham , Pearse A. Keane , Dan Milea , Christopher Chen , Tien Yin Wong , Vincent C.T. Mok , Carol Y. Cheung","doi":"10.1016/j.preteyeres.2024.101290","DOIUrl":"10.1016/j.preteyeres.2024.101290","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is the leading cause of dementia worldwide. Current diagnostic modalities of AD generally focus on detecting the presence of amyloid β and tau protein in the brain (for example, positron emission tomography [PET] and cerebrospinal fluid testing), but these are limited by their high cost, invasiveness, and lack of expertise. Retinal imaging exhibits potential in AD screening and risk stratification, as the retina provides a platform for the optical visualization of the central nervous system <em>in vivo</em>, with vascular and neuronal changes that mirror brain pathology.</p><p>Given the paradigm shift brought by advances in artificial intelligence and the emergence of disease-modifying therapies, this article aims to summarize and review the current literature to highlight 8 trends in an evolving landscape regarding the role and potential value of retinal imaging in AD screening.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"103 ","pages":"Article 101290"},"PeriodicalIF":18.6,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036838","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}
Benjamin WJ. Ng , Maria K. Kaukonen , Michelle E. McClements , Hoda Shamsnajafabadi , Robert E. MacLaren , Jasmina Cehajic-Kapetanovic
{"title":"Genetic therapies and potential therapeutic applications of CRISPR activators in the eye","authors":"Benjamin WJ. Ng , Maria K. Kaukonen , Michelle E. McClements , Hoda Shamsnajafabadi , Robert E. MacLaren , Jasmina Cehajic-Kapetanovic","doi":"10.1016/j.preteyeres.2024.101289","DOIUrl":"10.1016/j.preteyeres.2024.101289","url":null,"abstract":"<div><p>Conventional gene therapy involving supplementation only treats loss-of-function diseases and is limited by viral packaging sizes, precluding therapy of large genes. The discovery of CRISPR/Cas has led to a paradigm shift in the field of genetic therapy, with the promise of precise gene editing, thus broadening the range of diseases that can be treated. The initial uses of CRISPR/Cas have focused mainly on gene editing or silencing of abnormal variants via utilising Cas endonuclease to trigger the target cell endogenous non-homologous end joining. Subsequently, the technology has evolved to modify the Cas enzyme and even its guide RNA, leading to more efficient editing tools in the form of base and prime editing. Further advancements of this CRISPR/Cas technology itself have expanded its functional repertoire from targeted editing to programmable transactivation, shifting the therapeutic focus to precise endogenous gene activation or upregulation with the potential for epigenetic modifications. <em>In vivo</em> experiments using this platform have demonstrated the potential of CRISPR-activators (CRISPRa) to treat various loss-of-function diseases, as well as in regenerative medicine, highlighting their versatility to overcome limitations associated with conventional strategies. This review summarises the molecular mechanisms of CRISPRa platforms, the current applications of this technology <em>in vivo</em>, and discusses potential solutions to translational hurdles for this therapy, with a focus on ophthalmic diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"102 ","pages":"Article 101289"},"PeriodicalIF":18.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913765","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}
Linda M. Reis , Sarah E. Seese , Deborah Costakos , Elena V. Semina
{"title":"Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms","authors":"Linda M. Reis , Sarah E. Seese , Deborah Costakos , Elena V. Semina","doi":"10.1016/j.preteyeres.2024.101288","DOIUrl":"10.1016/j.preteyeres.2024.101288","url":null,"abstract":"<div><p>Development of the anterior segment of the eye requires reciprocal sequential interactions between the arising tissues, facilitated by numerous genetic factors. Disruption of any of these processes results in congenital anomalies in the affected tissue(s) leading to anterior segment disorders (ASD) including aniridia, Axenfeld-Rieger anomaly, congenital corneal opacities (Peters anomaly, cornea plana, congenital primary aphakia), and primary congenital glaucoma. Current understanding of the genetic factors involved in ASD remains incomplete, with approximately 50% overall receiving a genetic diagnosis. While some genes are strongly associated with a specific clinical diagnosis, the majority of known factors are linked with highly variable phenotypic presentations, with pathogenic variants in <em>FOXC1, CYP1B1,</em> and <em>PITX2</em> associated with the broadest spectrum of ASD conditions. This review discusses typical clinical presentations including associated systemic features of various forms of ASD; the latest functional data and genotype-phenotype correlations related to 25 ASD factors including newly identified genes; promising novel candidates; and current and emerging treatments for these complex conditions. Recent developments of interest in the genetics of ASD include identification of phenotypic expansions for several factors, discovery of multiple modes of inheritance for some genes, and novel mechanisms including a growing number of non-coding variants and alleles affecting specific domains/residues and requiring further studies.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"102 ","pages":"Article 101288"},"PeriodicalIF":18.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890021","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":"In vitro and ex vivo models of microbial keratitis: Present and future","authors":"Kelvin Kah Wai Cheng , Leonie Fingerhut , Sheelagh Duncan , N. Venkatesh Prajna , Adriano G. Rossi , Bethany Mills","doi":"10.1016/j.preteyeres.2024.101287","DOIUrl":"10.1016/j.preteyeres.2024.101287","url":null,"abstract":"<div><p>Microbial keratitis (MK) is an infection of the cornea, caused by bacteria, fungi, parasites, or viruses. MK leads to significant morbidity, being the fifth leading cause of blindness worldwide. There is an urgent requirement to better understand pathogenesis in order to develop novel diagnostic and therapeutic approaches to improve patient outcomes. Many <em>in vitro, ex vivo</em> and <em>in vivo</em> MK models have been developed and implemented to meet this aim. Here, we present current <em>in vitro</em> and <em>ex vivo</em> MK model systems, examining their varied design, outputs, reporting standards, and strengths and limitations. Major limitations include their relative simplicity and the perceived inability to study the immune response in these MK models, an aspect widely accepted to play a significant role in MK pathogenesis. Consequently, there remains a dependence on <em>in vivo</em> models to study this aspect of MK.</p><p>However, looking to the future, we draw from the broader field of corneal disease modelling, which utilises, for example, three-dimensional co-culture models and dynamic environments observed in bioreactors and organ-on-a-chip scenarios. These remain unexplored in MK research, but incorporation of these approaches will offer further advances in the field of MK corneal modelling, in particular with the focus of incorporation of immune components which we anticipate will better recapitulate pathogenesis and yield novel findings, therefore contributing to the enhancement of MK outcomes.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"102 ","pages":"Article 101287"},"PeriodicalIF":18.6,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000521/pdfft?md5=38c612dd2008abacdf08a18923b23280&pid=1-s2.0-S1350946224000521-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617054","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}
Gink N. Yang , Yu B.Y. Sun , Philip Ke Roberts , Hothri Moka , Min K. Sung , Jesse Gardner-Russell , Layal El Wazan , Bridget Toussaint , Satheesh Kumar , Heather Machin , Gregory J. Dusting , Geraint J. Parfitt , Kathryn Davidson , Elaine W. Chong , Karl D. Brown , Jose M. Polo , Mark Daniell
{"title":"Exploring single-cell RNA sequencing as a decision-making tool in the clinical management of Fuchs’ endothelial corneal dystrophy","authors":"Gink N. Yang , Yu B.Y. Sun , Philip Ke Roberts , Hothri Moka , Min K. Sung , Jesse Gardner-Russell , Layal El Wazan , Bridget Toussaint , Satheesh Kumar , Heather Machin , Gregory J. Dusting , Geraint J. Parfitt , Kathryn Davidson , Elaine W. Chong , Karl D. Brown , Jose M. Polo , Mark Daniell","doi":"10.1016/j.preteyeres.2024.101286","DOIUrl":"10.1016/j.preteyeres.2024.101286","url":null,"abstract":"<div><p>Single-cell RNA sequencing (scRNA-seq) has enabled the identification of novel gene signatures and cell heterogeneity in numerous tissues and diseases. Here we review the use of this technology for Fuchs’ Endothelial Corneal Dystrophy (FECD). FECD is the most common indication for corneal endothelial transplantation worldwide. FECD is challenging to manage because it is genetically heterogenous, can be autosomal dominant or sporadic, and progress at different rates. Single-cell RNA sequencing has enabled the discovery of several FECD subtypes, each with associated gene signatures, and cell heterogeneity. Current FECD treatments are mainly surgical, with various Rho kinase (ROCK) inhibitors used to promote endothelial cell metabolism and proliferation following surgery. A range of emerging therapies for FECD including cell therapies, gene therapies, tissue engineered scaffolds, and pharmaceuticals are in preclinical and clinical trials. Unlike conventional disease management methods based on clinical presentations and family history, targeting FECD using scRNA-seq based precision-medicine has the potential to pinpoint the disease subtypes, mechanisms, stages, severities, and help clinicians in making the best decision for surgeries and the applications of therapeutics. In this review, we first discuss the feasibility and potential of using scRNA-seq in clinical diagnostics for FECD, highlight advances from the latest clinical treatments and emerging therapies for FECD, integrate scRNA-seq results and clinical notes from our FECD patients and discuss the potential of applying alternative therapies to manage these cases clinically.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"102 ","pages":"Article 101286"},"PeriodicalIF":18.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538505","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}
Bhakta Prasad Gaire, Yosef Koronyo, Dieu-Trang Fuchs, Haoshen Shi, Altan Rentsendorj, Ron Danziger, Jean-Philippe Vit, Nazanin Mirzaei, Jonah Doustar, Julia Sheyn, Harald Hampel, Andrea Vergallo, Miyah R Davis, Ousman Jallow, Filippo Baldacci, Steven R Verdooner, Ernesto Barron, Mehdi Mirzaei, Vivek K Gupta, Stuart L Graham, Mourad Tayebi, Roxana O Carare, Alfredo A Sadun, Carol A Miller, Oana M Dumitrascu, Shouri Lahiri, Liang Gao, Keith L Black, Maya Koronyo-Hamaoui
{"title":"Alzheimer's disease pathophysiology in the Retina.","authors":"Bhakta Prasad Gaire, Yosef Koronyo, Dieu-Trang Fuchs, Haoshen Shi, Altan Rentsendorj, Ron Danziger, Jean-Philippe Vit, Nazanin Mirzaei, Jonah Doustar, Julia Sheyn, Harald Hampel, Andrea Vergallo, Miyah R Davis, Ousman Jallow, Filippo Baldacci, Steven R Verdooner, Ernesto Barron, Mehdi Mirzaei, Vivek K Gupta, Stuart L Graham, Mourad Tayebi, Roxana O Carare, Alfredo A Sadun, Carol A Miller, Oana M Dumitrascu, Shouri Lahiri, Liang Gao, Keith L Black, Maya Koronyo-Hamaoui","doi":"10.1016/j.preteyeres.2024.101273","DOIUrl":"10.1016/j.preteyeres.2024.101273","url":null,"abstract":"<p><p>The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":" ","pages":"101273"},"PeriodicalIF":18.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958900","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}