Pub Date : 2024-09-06DOI: 10.1016/j.preteyeres.2024.101299
Elena K Schneider-Futschik, Yimin Zhu, Danni Li, Mark D Habgood, Bao N Nguyen, Ines Pankonien, Margarida Amaral, Laura E Downie, Holly R Chinnery
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 trials have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of 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 possible role of CFTR in the developing 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.
{"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 Amaral, Laura E Downie, Holly R Chinnery","doi":"10.1016/j.preteyeres.2024.101299","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101299","url":null,"abstract":"<p><p>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 trials have largely overlooked the potential for ocular disturbances with CFTR modulator therapy, with the exception of a few case studies reporting the presence of 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 possible role of CFTR in the developing 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.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":null,"pages":null},"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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-30DOI: 10.1016/j.preteyeres.2024.101292
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.
{"title":"Optical coherence tomography angiography of the retina and choroid in systemic diseases","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-08-24DOI: 10.1016/j.preteyeres.2024.101291
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.
{"title":"The AI revolution in glaucoma: Bridging challenges with opportunities","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-08-22DOI: 10.1016/j.preteyeres.2024.101290
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 in vivo, with vascular and neuronal changes that mirror brain pathology.
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.
{"title":"Value proposition of retinal imaging in Alzheimer's disease screening: A review of eight evolving trends","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-08-08DOI: 10.1016/j.preteyeres.2024.101289
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. In vivo 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 in vivo, and discusses potential solutions to translational hurdles for this therapy, with a focus on ophthalmic diseases.
传统的补充基因疗法只能治疗功能缺失性疾病,而且受到病毒包装大小的限制,无法治疗大基因。CRISPR/Cas 的发现带来了基因治疗领域的范式转变,有望实现精确的基因编辑,从而扩大可治疗疾病的范围。CRISPR/Cas 的最初用途主要集中在利用 Cas 内切酶触发靶细胞内源性非同源末端连接,从而对异常变异进行基因编辑或沉默。随后,该技术不断发展,对 Cas 酶甚至其引导 RNA 进行了修改,从而产生了更有效的碱基和质粒编辑工具。CRISPR/Cas 技术本身的进一步发展扩大了其功能范围,从定向编辑到可编程转录激活,将治疗重点转移到精确的内源性基因激活或上调,并有可能进行表观遗传修饰。利用这一平台进行的体内实验证明,CRISPR-激活剂(CRISPRa)具有治疗各种功能缺失性疾病和再生医学的潜力,突出了其克服传统策略局限性的多功能性。这篇综述总结了CRISPRa平台的分子机制、这一技术目前在体内的应用,并讨论了这一疗法在转化障碍方面的潜在解决方案,重点关注眼科疾病。
{"title":"Genetic therapies and potential therapeutic applications of CRISPR activators in the eye","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-08-02DOI: 10.1016/j.preteyeres.2024.101288
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 FOXC1, CYP1B1, and PITX2 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.
{"title":"Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-07-14DOI: 10.1016/j.preteyeres.2024.101287
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 in vitro, ex vivo and in vivo MK models have been developed and implemented to meet this aim. Here, we present current in vitro and ex vivo 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 in vivo models to study this aspect of MK.
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.
{"title":"In vitro and ex vivo models of microbial keratitis: Present and future","authors":"","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":null,"pages":null},"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}
Pub Date : 2024-07-03DOI: 10.1016/j.preteyeres.2024.101286
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
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.
{"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":null,"pages":null},"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}
Pub Date : 2024-07-01Epub Date: 2024-05-15DOI: 10.1016/j.preteyeres.2024.101273
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
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.
视网膜是一种新兴的中枢神经系统靶点,可用于阿尔茨海默病(AD)的潜在无创诊断和追踪。研究已在阿尔茨海默病患者和动物模型的视网膜中发现了阿尔茨海默病的病理特征,包括淀粉样β蛋白(Aβ)沉积和 tau 蛋白异构体异常。此外,在轻度认知障碍和 AD 痴呆症患者的视网膜中也发现了血管结构和功能异常,如血流量减少、血管 Aβ 沉积、血液-视网膜屏障损伤,以及炎症和神经变性。组织学、生物化学和临床研究表明,视网膜和大脑中的 AD 病变的性质和严重程度是一致的。蛋白质组学分析表明,AD 患者视网膜和大脑中的蛋白质和生物通路的失调模式相似,炎症和神经退行性过程增强,氧化磷酸化受损,线粒体功能障碍。值得注意的是,研究性成像技术现在可以检测到 AD 特异性淀粉样蛋白沉积,以及在世 AD 患者视网膜中的血管病变和神经变性,这表明不同疾病阶段的改变以及与大脑病理学的联系。光学相干断层扫描(OCT)、OCT 血管造影术、共焦扫描激光眼底镜和高光谱成像等当前和探索性的眼科成像模式可能会为 AD 的临床评估带来希望。然而,我们还需要进一步的研究来加深了解注意力缺失症对视网膜的影响及其进展。为了推动这一领域的研究,未来的研究需要在更大范围和更多样化的群体中进行复制,并使用已确认的注意力缺失症生物标志物和标准化视网膜成像技术。这将验证潜在的注意力缺失症视网膜生物标志物,有助于早期筛查和监测。
{"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":null,"pages":null},"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}
Pub Date : 2024-07-01Epub Date: 2024-05-16DOI: 10.1016/j.preteyeres.2024.101272
Oliver R Marmoy, Manca Tekavčič Pompe, Jan Kremers
Objective assessment of the visual system can be performed electrophysiologically using the visual evoked potential (VEP). In many clinical circumstances, this is performed using high contrast achromatic patterns or diffuse flash stimuli. These methods are clinically valuable but they may only assess a subset of possible physiological circuitries within the visual system, particularly those involved in achromatic (luminance) processing. The use of chromatic VEPs (cVEPs) in addition to standard VEPs can inform us of the function or dysfunction of chromatic pathways. The chromatic VEP has been well studied in human health and disease. Yet, to date our knowledge of their underlying mechanisms and applications remains limited. This likely reflects a heterogeneity in the methodology, analysis and conclusions of different works, which leads to ambiguity in their clinical use. This review sought to identify the primary methodologies employed for recording cVEPs. Furthermore cVEP maturation and application in understanding the function of the chromatic system under healthy and diseased conditions are reviewed. We first briefly describe the physiology of normal colour vision, before describing the methodologies and historical developments which have led to our understanding of cVEPs. We thereafter describe the expected maturation of the cVEP, followed by reviewing their application in several disorders: congenital colour vision deficiencies, retinal disease, glaucoma, optic nerve and neurological disorders, diabetes, amblyopia and dyslexia. We finalise the review with recommendations for testing and future directions.
{"title":"Chromatic visual evoked potentials: A review of physiology, methods and clinical applications.","authors":"Oliver R Marmoy, Manca Tekavčič Pompe, Jan Kremers","doi":"10.1016/j.preteyeres.2024.101272","DOIUrl":"10.1016/j.preteyeres.2024.101272","url":null,"abstract":"<p><p>Objective assessment of the visual system can be performed electrophysiologically using the visual evoked potential (VEP). In many clinical circumstances, this is performed using high contrast achromatic patterns or diffuse flash stimuli. These methods are clinically valuable but they may only assess a subset of possible physiological circuitries within the visual system, particularly those involved in achromatic (luminance) processing. The use of chromatic VEPs (cVEPs) in addition to standard VEPs can inform us of the function or dysfunction of chromatic pathways. The chromatic VEP has been well studied in human health and disease. Yet, to date our knowledge of their underlying mechanisms and applications remains limited. This likely reflects a heterogeneity in the methodology, analysis and conclusions of different works, which leads to ambiguity in their clinical use. This review sought to identify the primary methodologies employed for recording cVEPs. Furthermore cVEP maturation and application in understanding the function of the chromatic system under healthy and diseased conditions are reviewed. We first briefly describe the physiology of normal colour vision, before describing the methodologies and historical developments which have led to our understanding of cVEPs. We thereafter describe the expected maturation of the cVEP, followed by reviewing their application in several disorders: congenital colour vision deficiencies, retinal disease, glaucoma, optic nerve and neurological disorders, diabetes, amblyopia and dyslexia. We finalise the review with recommendations for testing and future directions.</p>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":null,"pages":null},"PeriodicalIF":18.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958904","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}