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Is Caveolin-1 Required for Retinal Neuroprotection?
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_47
Olawale O Bankole, Michael H Elliott
{"title":"Is Caveolin-1 Required for Retinal Neuroprotection?","authors":"Olawale O Bankole, Michael H Elliott","doi":"10.1007/978-3-031-76550-6_47","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_47","url":null,"abstract":"<p><p>The innate ability to produce neurotrophic cytokines is a crucial component of retinal neuroprotection. Reduced levels of these cytokines accelerate neuronal cell death in the retina during injury but prolonged overexpression can lead to inflammation and retinal damage. It is therefore critical to find molecular targets that regulate the endogenous production of retinal neurotrophic factors. Outside of the eye, caveolins play essential roles in preconditioning, pro-survival signaling, and neuronal protection. They amplify the secretion of neuroprotective cytokines such as leukemia inhibitory factor (LIF), an important retinal neurotroph. We hypothesize that Caveolin-1 (Cav1) in the retina is required for retinal neuroprotection. This mini-review summarizes findings on the cytoprotective roles of Cav1 and how it may be required for retinal neuroprotection.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"287-291"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Extracellular Matrix Gene Expression Patterns in Retinal Wound Healing: A Comparative Study Between Mouse and Zebrafish Laser Injury Models.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_35
Laura Jahnke, Volker Enzmann
{"title":"Extracellular Matrix Gene Expression Patterns in Retinal Wound Healing: A Comparative Study Between Mouse and Zebrafish Laser Injury Models.","authors":"Laura Jahnke, Volker Enzmann","doi":"10.1007/978-3-031-76550-6_35","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_35","url":null,"abstract":"<p><p>Fibrosis is an outcome of irregular wound healing, manifesting as heightened scar formation marked by substantial extracellular matrix (ECM) accumulation, persistent inflammation, and gradual tissue or organ restructuring. This condition disrupts the normal tissue architecture, impairing organ function. Herein, the pivotal role of fibrosis in retinal repair mechanisms is compared in mice and zebrafish in responses to laser-induced injury. Our focus spans the intricate interplay between the gene regulation of ECM-involved protagonists and the dynamic development of fibrotic scars. We observed differential gene expression shifts and evaluated the effects of the fibrosis inhibitor pirfenidone (PFD) in the mouse model. These insights into retinal repair mechanisms contribute to a comprehensive understanding, guiding future therapeutic strategies for vision preservation.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"213-217"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Late-Onset Retinal Degeneration: Clinical Features and C1QTNF5/CTRP5 Function.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_83
Ana Alonso-Carriazo Fernández, Amanda-Jayne F Carr
{"title":"Late-Onset Retinal Degeneration: Clinical Features and C1QTNF5/CTRP5 Function.","authors":"Ana Alonso-Carriazo Fernández, Amanda-Jayne F Carr","doi":"10.1007/978-3-031-76550-6_83","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_83","url":null,"abstract":"<p><p>Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant inherited macular disease caused by mutations in C1QTNF5 (CTRP5). While pathophysiological features vary, patients often present yellow-white punctate lesions and sub-RPE deposits. Multiple in silico, in vitro and in vivo studies have investigated the molecular mechanisms by which C1QTNF5 mutations lead to L-ORD. This review summarises key clinical findings and clinical management of L-ORD and focuses on what is known about the C1QNTF5 gene, protein structure and function, in health and disease.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"511-516"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ocular Localization of Complement Factor H and Its Association with Diseases in the Eye.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_71
Rayne R Lim, Jennifer R Chao
{"title":"Ocular Localization of Complement Factor H and Its Association with Diseases in the Eye.","authors":"Rayne R Lim, Jennifer R Chao","doi":"10.1007/978-3-031-76550-6_71","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_71","url":null,"abstract":"<p><p>The complement system is a well-documented element of the immune system that protects the body from external pathogens. Although the majority of complement components are produced by the liver and secreted into the circulation, ocular tissues also produce several complement components, thereby contributing to local complement activity in specific regions of the eye. Regulation of complement cascade activation is crucial for preventing unintended cellular damage. In the alternative pathway of the complement system, complement factor H (CFH) plays an important role in inhibitory regulation. Certain genetic polymorphisms that result in defective CFH are associated with rare diseases where the self is attacked by an overactive complement system. This review will focus on the expression and localization of CFH in human ocular tissues and highlight its association with several diseases in the anterior and posterior chambers of the eye.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"435-439"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_27
Tanu Parmar, Vipul Parmar, Goldis Malek
{"title":"Potential Role of NUR77 in the Aging Retinal Pigment Epithelium and Age-Related Macular Degeneration.","authors":"Tanu Parmar, Vipul Parmar, Goldis Malek","doi":"10.1007/978-3-031-76550-6_27","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_27","url":null,"abstract":"<p><p>The underlying mechanisms associated with age-related changes in the morphology and function of retinal pigmented epithelial (RPE) cells are poorly understood. The aging RPE progresses through several structural changes including loss of melanin granules, accumulation of lipofuscin, and cytoskeletal changes, among others. Extracellular to it, there is also thickening of Bruch's membrane and changes in the integrity of the choroid. Recent studies have revealed that aging also affects the metabolic ecosystem of the RPE. Aged mitochondria exhibit decreased rates of oxidative phosphorylation, increased reactive oxygen species generation, and increased number of mitochondrial mutations relative to baseline. These changes are also found in age-related macular degeneration (AMD), a late-onset vision-impairing disease, in which the RPE is particularly vulnerable. The orphan nuclear receptor NR4A1/NUR77 is an early response gene and regulator of various cellular processes during development, aging, and disease. Previously we observed decreased levels of Nur77/NUR77 in both mouse and human RPE as a function of age. Current knowledge of the function of this receptor in the RPE is limited. Herein, we discuss the putative roles of NUR77 in the RPE during aging and disease.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"165-169"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial Intelligence-Assisted Matching of Human Postmortem Donors to Ocular Research Projects.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_82
Gregory H Grossman, Thomas Cattell, Alyssa Abbott, Daniel MacIntyre
{"title":"Artificial Intelligence-Assisted Matching of Human Postmortem Donors to Ocular Research Projects.","authors":"Gregory H Grossman, Thomas Cattell, Alyssa Abbott, Daniel MacIntyre","doi":"10.1007/978-3-031-76550-6_82","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_82","url":null,"abstract":"<p><p>The scarcity of human ocular samples with short postmortem intervals (PMIs) is a significant issue in ophthalmic research and drug discovery. A contributing factor is that eye banks must manually match donor data to prospective research project criteria, which is time-consuming, inefficient, and error-prone. We have previously reported on the successful use of a semi-automated matching system, ReSync. The barrier to full autonomy is that donor medical data is often provided as unstructured data in free text fields, which prevents interoperability with matching databases. Herein, we report on a small retrospective study, in which artificial intelligence (AI) is incorporated into ReSync (ReSyncAI) to test AI's ability to structure donor data for subsequent matching. From a set of historical cases, medical data was securely sent to a large language model with natural language processing. After structuring and standardizing, data was returned to ReSync for analysis and match testing. A 94.2% success rate in medical terminology keyword extraction in concert with correcting and standardizing medical data was achieved. Structured data was fully interoperable with ReSync. In a subset of cases, ReSyncAI properly matched donors to the standardized term of \"age-related macular degeneration\" from donor data, including instances of abbreviations, misspellings, and incomplete designations.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"505-509"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uncovering Novel Drugs that Restore Vision Using Orthogonal Pooling in Zebrafish.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_80
Justine O'Brien, Patrizia Colucci, Yolanda Alvarez, Breandán N Kennedy
{"title":"Uncovering Novel Drugs that Restore Vision Using Orthogonal Pooling in Zebrafish.","authors":"Justine O'Brien, Patrizia Colucci, Yolanda Alvarez, Breandán N Kennedy","doi":"10.1007/978-3-031-76550-6_80","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_80","url":null,"abstract":"<p><p>Photoreceptor and retinal pigment epithelium (RPE) dysfunction in inherited retinal degenerations (IRDs) and age-related macular degeneration (AMD) necessitate innovative therapies to preserve vision. Vision impairment incurs a substantial global economic burden, with the World Health Organization reporting an annual global productivity loss of approximately $411 billion. Current treatments are limited, underscoring the urgency for novel solutions. Leveraging new screening techniques, novel drugs restoring vision can be uncovered. Here, a workflow is described utilising orthogonal pooling to screen randomised library compounds for drug hits restoring vision and assessing the optokinetic response (OKR) in the atp6v0e1<sup>-/-</sup> zebrafish model of inherited blindness.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"491-495"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expression of Versican in the Retina and Its Implication in Retinal Disease.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_69
Andrea E Dillinger, Anja K Hoffmann, Ernst R Tamm
{"title":"Expression of Versican in the Retina and Its Implication in Retinal Disease.","authors":"Andrea E Dillinger, Anja K Hoffmann, Ernst R Tamm","doi":"10.1007/978-3-031-76550-6_69","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_69","url":null,"abstract":"<p><p>Chondroitin sulfate proteoglycans are characterized by their sulfated glycosaminoglycan chains covalently attached to the core protein. Versican, encoded by the CSPG2 gene, is a chondroitin sulfate proteoglycan highly expressed in the human and mouse retina. Due to alternative splicing, it exists in four different isoforms: V0, V1, V2 and V3. Interactions with a variety of proteins lead to its main functions, such as influencing cellular adhesion, migration, proliferation and regulating inflammatory processes. Versican expression is high during retinal development and decreases in the mature tissue, remaining mostly in the retinal pigment epithelium, Bruch's membrane and choroid blood vessel walls. Mutations in the CSPG2 gene resulting in an imbalance of Versican splice variants cause erosive vitreoretinopathy and Wagner disease. Its regulatory role in a variety of functions, especially those influencing extracellular matrix composition and inflammation, suggests a crucial role in the pathomechanisms of retinal degenerative disorders and should be the purpose of future research.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"423-427"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_15
Hossein Ameri, Niranjana Kesavamoorthy, Dara N Bruce
{"title":"Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases.","authors":"Hossein Ameri, Niranjana Kesavamoorthy, Dara N Bruce","doi":"10.1007/978-3-031-76550-6_15","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_15","url":null,"abstract":"<p><p>This study describes worldwide gene therapy clinical trials aimed at treating inherited retinal diseases (IRD). The information was collected through 15 different international registries including clinicaltrials.gov . There have been 101 gene therapy clinical trials targeting IRD up until the end of 2022. Seventy-seven trials employed gene augmentation using viral vectors; other approaches included inhibitory RNA (9), encapsulated cell technology (6), systemic approach (1), and observational trials (8). The most common clinical trial phase was phase 1/2 (46), followed by phase 3 (12). One trial led to an FDA-approved treatment. Sixty-nine trials were conducted in a single country, and 32 trials were multinational; The USA had the highest share in both categories. Retinitis pigmentosa was the most common disease targeted (39), followed by RPE65-mediated retinal dystrophy (13), Leber hereditary optic neuropathy (13), choroideremia (10 and achromatopsia (8), Leber congenital amaurosis (4), X-linked retinoschisis (4), Stargardt disease (4), Bietti's crystalline dystrophy (2), autosomal dominant optic atrophy (1), and Gyrate atrophy (1). For gene augmentation trials, adeno-associated virus was the most commonly used viral vector (70 trials-90%).</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"89-93"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Calcium-Binding Protein 4 Is Fundamental for Retinal Structure and Function.
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_33
Billie Beckwith-Cohen, Simon M Petersen-Jones
{"title":"Calcium-Binding Protein 4 Is Fundamental for Retinal Structure and Function.","authors":"Billie Beckwith-Cohen, Simon M Petersen-Jones","doi":"10.1007/978-3-031-76550-6_33","DOIUrl":"https://doi.org/10.1007/978-3-031-76550-6_33","url":null,"abstract":"<p><p>Calcium-binding proteins (CaBPs) are a subfamily of calmodulin-like proteins, that modulate presynaptic calcium-dependent interactions with voltage-gated calcium channels. CaBPs play crucial roles in the development of normal sensorineural structure and function in both the visual and auditory systems. Disruption of CaBPs can result in a range of synaptic disorders of varying severity, which are dependent on the proteins or isoforms that predominate the affected system. In the retina, CaBP4 seems to be the isoform that is most important for the development of structure and function of the photoreceptor to ON bipolar synapse. Absence of CaBP4 results in synaptic ribbon immaturity in the first retinal synapse, disruption of ON-bipolar cell-driven responses, and a structurally thin outer plexiform layer. It has recently been demonstrated that at least some of the functional and anatomic disruption caused by CaBP mutations can be successfully addressed with gene augmentation therapy both in the eye and ear.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"203-206"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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