Frontiers in ophthalmology最新文献_第8页

Unlocking the role of lactate: metabolic pathways, signaling, and gene regulation in postmitotic retinal cells 解锁乳酸的作用:有丝分裂后视网膜细胞的代谢途径、信号传导和基因调控

Frontiers in ophthalmology Pub Date : 2023-11-08 DOI: 10.3389/fopht.2023.1296624

Raju V. S. Rajala, Ammaji Rajala

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Editorial: Translational opportunities for AI in glaucoma. 社论：人工智能在青光眼领域的转化机遇。

Frontiers in ophthalmology Pub Date : 2023-11-06 eCollection Date: 2023-01-01 DOI: 10.3389/fopht.2023.1299582

Kevin C Chan, Rebecca M Sappington

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Topical ocular application of aggrelyte-2A reduces lens stiffness in mice 局部眼内应用aggrelyte-2A可降低小鼠晶状体硬度

Frontiers in ophthalmology Pub Date : 2023-10-31 DOI: 10.3389/fopht.2023.1274825

Sudipta Panja, Mi-Hyun Nam, Hanmant Gaikwad, Johanna Rankenberg, Ram H. Nagaraj

{"title":"Topical ocular application of aggrelyte-2A reduces lens stiffness in mice","authors":"Sudipta Panja, Mi-Hyun Nam, Hanmant Gaikwad, Johanna Rankenberg, Ram H. Nagaraj","doi":"10.3389/fopht.2023.1274825","DOIUrl":"https://doi.org/10.3389/fopht.2023.1274825","url":null,"abstract":"Presbyopia is the progressive loss of the ability of the lens to focus on nearby objects due to its increased stiffness. It occurs in the mid-40s and continues to worsen until the mid-60s. The age-associated increase in protein cross-linking in the lens leads to protein aggregation and water insolubility, especially in the nuclear region, contributing to lens stiffness. This study reports the development of aggrelyte-2A (methyl S -acetyl- N -(3,3-dimethylbutanoyl) cysteinate, a derivative of our previously reported aggrelyte-2) for reversing the stiffness of aged lenses. Aggrelyte-2A showed minimal toxicity in cultured mouse lens epithelial cells (up to 2000 µM) and human lens epithelial cells (up to 250 µM). Lenses from aged mice (age: 24-25 months) treated with 1 mM aggrelyte-2A for 24 h, and human lenses (age: 47-67 years) treated with 250 µM aggrelyte-2A for 48 h showed 11-14% reductions in stiffness, accompanied by an increase in acetyllysine in lens proteins, and free-thiols in the lens. Topical application of aggrelyte-2A (40 mM, 5 µl twice daily for 4 weeks) on mouse eyes significantly reduced lens stiffness. The topical application showed no toxicity to the lens, cornea, or retina, as revealed by morphological examination, H&amp;E staining, and optical coherence tomography. These data suggest that aggrelyte-2A could be developed as a presbyopia-reversing therapeutic.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135813694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume 严格6°倒立卧床时视盘水肿与单碳代谢途径遗传和视杯容积有关

Frontiers in ophthalmology Pub Date : 2023-10-27 DOI: 10.3389/fopht.2023.1279831

Sara R. Zwart, Brandon R. Macias, Steven S. Laurie, Connor Ferguson, Claudia Stern, Alex Suh, M. Mark Melin, Millennia Young, Eric Bershad, Scott M. Smith

{"title":"Optic disc edema during strict 6° head-down tilt bed rest is related to one-carbon metabolism pathway genetics and optic cup volume","authors":"Sara R. Zwart, Brandon R. Macias, Steven S. Laurie, Connor Ferguson, Claudia Stern, Alex Suh, M. Mark Melin, Millennia Young, Eric Bershad, Scott M. Smith","doi":"10.3389/fopht.2023.1279831","DOIUrl":"https://doi.org/10.3389/fopht.2023.1279831","url":null,"abstract":"Some astronauts on International Space Station missions experience neuroophthalmological pathologies as part of spaceflight associated neuro-ocular syndrome (SANS). Strict head-down tilt bed rest (HDTBR) is a spaceflight analog that replicates SANS findings and those who had 3–4 risk alleles (G and C alleles from the methionine synthase reductase [MTRR] A66G and serine hydroxymethyltransferase [SHMT1] C1420T, respectively) as compared to 1-2 risk alleles, had a greater increase in total retinal thickness (TRT). The objective of this study was to identify factors that contribute to the individual variability of the development of SANS in a 60 d HDTBR at the German Aerospace Center’s:envihab facility, Cologne Germany. 22 of 24 subjects who participated in the HDTBR study provided blood samples for genetic analysis. Total retinal thickness and optic cup volume were measured before and after bed rest. Subjects with 3–4 versus 0-2 risk alleles had greater ΔTRT during and after bed rest, and the model improved with the addition of baseline optic cup volume. This bed rest study confirms that variants of MTRR and SHMT1 are associated with ocular pathologies. Subjects with more risk alleles had the greatest HDTBR-induced ΔTRT, reaffirming that genetics predispose some individuals to developing SANS. Preflight optic cup volume and genetics better predict ΔTRT than either one alone. Whether nutritional supplements can override the genetic influences on biochemistry, physiology, and pathophysiology remains to be tested. These findings have significant implications for both aerospace and terrestrial medicine.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136317601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Dehydroalanine and dehydrobutyrine in aging and cataractous lenses reveal site-specific consequences of spontaneous protein degradation 老化和白内障晶状体中的脱氢丙氨酸和脱氢丁氨酸揭示了自发蛋白质降解的位点特异性后果

Frontiers in ophthalmology Pub Date : 2023-10-26 DOI: 10.3389/fopht.2023.1241001

Jessica Paredes, Zhen Wang, Purvi Patel, Kristie L. Rose, Kevin L. Schey

{"title":"Dehydroalanine and dehydrobutyrine in aging and cataractous lenses reveal site-specific consequences of spontaneous protein degradation","authors":"Jessica Paredes, Zhen Wang, Purvi Patel, Kristie L. Rose, Kevin L. Schey","doi":"10.3389/fopht.2023.1241001","DOIUrl":"https://doi.org/10.3389/fopht.2023.1241001","url":null,"abstract":"Introduction Protein post-translational modifications (PTMs) have been associated with aging and age-related diseases. PTMs are particularly impactful in long-lived proteins, such as those found in the ocular lens, because they accumulate with age. Two PTMs that lead to protein-protein crosslinks in aged and cataractous lenses are dehydroalanine (DHA) and dehydrobutyrine (DHB); formed from cysteine/serine and threonine residues, respectively. The purpose of this study was to quantitate DHA and DHB in human lens proteins as a function of age and cataract status. Methods Human lenses of various ages were divided into five donor groups: transparent lenses (18–22-year-old, 48–64-year-old, and 70–93-year-old) and cataractous human lenses of two age groups (48–64-year-old lenses, and 70–93-year-old lenses) and were subjected to proteomic analysis. Relative DHA and DHB peptide levels were quantified and compared to their non-modified peptide counterparts. Results For most lens proteins containing DHA or DHB, higher amounts of DHA- and DHB-modified peptides were detected in aged and cataractous lenses. DHA-containing peptides were classified into three groups based on abundance changes with age and cataract: those that (1) increased only in age-related nuclear cataract (ARNC), (2) increased in aged and cataractous lenses, and (3) decreased in aged lenses and ARNC. There was no indication that DHA or DHB levels were dependent on lens region. In most donor groups, proteins with DHA and DHB were more likely to be found among urea-insoluble proteins rather than among water- or urea-soluble proteins. Discussion DHA and DHB formation may induce structural effects that make proteins less soluble in water that leads to age-related protein insolubility and possibly aggregation and light scattering.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134908689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Role of integrins in the development of fibrosis in the trabecular meshwork 整合素在小梁网纤维化发展中的作用

Frontiers in ophthalmology Pub Date : 2023-10-24 DOI: 10.3389/fopht.2023.1274797

Jennifer A. Faralli, Mark S. Filla, Donna M. Peters

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Editorial: In vivo retinal imaging in animal models 社论：动物模型的活体视网膜成像

Frontiers in ophthalmology Pub Date : 2023-10-23 DOI: 10.3389/fopht.2023.1309894

Tae-Hoon Kim, Y. Paulus, Bernhard Baumann, Pengfei Zhang, Shaohua Pi

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Paving the way while playing catch up: mitochondrial genetics in African ancestry primary open-angle glaucoma 在追赶的同时铺平道路:非洲祖先原发性开角型青光眼的线粒体遗传学

Frontiers in ophthalmology Pub Date : 2023-10-12 DOI: 10.3389/fopht.2023.1267119

Grace Kuang, Rebecca Salowe, Joan O’Brien

{"title":"Paving the way while playing catch up: mitochondrial genetics in African ancestry primary open-angle glaucoma","authors":"Grace Kuang, Rebecca Salowe, Joan O’Brien","doi":"10.3389/fopht.2023.1267119","DOIUrl":"https://doi.org/10.3389/fopht.2023.1267119","url":null,"abstract":"Glaucoma, the leading cause of irreversible blindness worldwide, disproportionately affects individuals of African descent. Specifically, previous research has indicated that primary open-angle glaucoma (POAG), the most common form of disease, is more prevalent, severe, early-onset, and rapidly-progressive in populations of African ancestry. Recent studies have identified genetic variations that may contribute to the greater burden of disease in this population. In particular, mitochondrial genetics has emerged as a profoundly influential factor in multiple neurodegenerative diseases, including POAG. Several hypotheses explaining the underlying mechanisms of mitochondrial genetic contribution to disease progression have been proposed, including nuclear-mitochondrial gene mismatch. Exploring the fundamentals of mitochondrial genetics and disease pathways within the understudied African ancestry population can lead to groundbreaking advancements in the research and clinical understanding of POAG. This article discusses the currently known involvements of mitochondrial genetic factors in POAG, recent directions of study, and potential future prospects in mitochondrial genetic studies in individuals of African descent.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136014610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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The effects of a highly bioavailable curcumin PhytosomeTM preparation on the retinal architecture and glial reactivity in the GFAP-IL6 mice 高生物利用度姜黄素PhytosomeTM制剂对gmap - il6小鼠视网膜结构和神经胶质反应性的影响

Frontiers in ophthalmology Pub Date : 2023-10-06 DOI: 10.3389/fopht.2023.1205542

Víctor Pérez-Fernández, Akshaya Lakshmi Thananjeyan, Faheem Ullah, Gerald Münch, Morven Cameron, Erika Gyengesi

{"title":"The effects of a highly bioavailable curcumin PhytosomeTM preparation on the retinal architecture and glial reactivity in the GFAP-IL6 mice","authors":"Víctor Pérez-Fernández, Akshaya Lakshmi Thananjeyan, Faheem Ullah, Gerald Münch, Morven Cameron, Erika Gyengesi","doi":"10.3389/fopht.2023.1205542","DOIUrl":"https://doi.org/10.3389/fopht.2023.1205542","url":null,"abstract":"Uncontrolled, chronic inflammation in the retina can disturb retinal structure and function leading to impaired visual function. For the first time, in a mouse model of chronic neuroinflammation (GFAP-IL6), we investigated the impact of chronic glial activation on the retinal microglia population and structure. In addition, we tested a curcumin Phytosome TM preparation with enhanced bioavailability to investigate the effects of a cytokine-suppressing anti-inflammatory drug on retinal architecture. Curcumin Phytosome TM was fed to 3-month old GFAP-IL6 mice for 4 weeks and compared to their untreated GFAP-IL6 counterparts as well as wild type mice on control diet. Microglial numbers and morphology together with neuronal numbers were characterized using immunohistochemistry and cell reconstruction in the retina, using retinal wholemount and slices. GFAP-IL6 mice showed a significant increase in Iba1-labelled mononuclear phagocytes, including microglia, and displayed altered glial morphology. This resulted in a reduction in cone density and a thinning of the retinal layers compared to wild type mice. Curcumin Phytosome TM treatment contributed to decreased microglial density, significantly decreasing both soma and cell size compared to control diet, as well as preventing the thinning of the retinal layers. This study is the first to characterize the impact of chronic retinal inflammation in the GFAP-IL6 mouse and the therapeutic benefit of enhanced bioavailable curcumin Phytosome TM to significantly reduce microglia density and prevent neuronal loss. These data suggest that curcumin could be used as a complementary therapy alongside traditional treatments to reduce associated retinal inflammation in a variety of retinal diseases.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135303105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of the extracellular vesicle proteome between glaucoma and non-glaucoma trabecular meshwork cells 青光眼与非青光眼小梁网细胞胞外囊泡蛋白质组的比较

Frontiers in ophthalmology Pub Date : 2023-10-06 DOI: 10.3389/fopht.2023.1257737

Fiona S. McDonnell, Bre’Ida J. Riddick, Haven Roberts, Nikolai Skiba, W. Daniel Stamer

{"title":"Comparison of the extracellular vesicle proteome between glaucoma and non-glaucoma trabecular meshwork cells","authors":"Fiona S. McDonnell, Bre’Ida J. Riddick, Haven Roberts, Nikolai Skiba, W. Daniel Stamer","doi":"10.3389/fopht.2023.1257737","DOIUrl":"https://doi.org/10.3389/fopht.2023.1257737","url":null,"abstract":"Introduction Extracellular matrix (ECM) materials accumulate in the trabecular meshwork (TM) tissue of patients with glaucoma, which is associated with a decrease in aqueous humor outflow and therefore an increase in intraocular pressure. To explore a potential mechanism for ECM regulation in the TM, we purified extracellular vesicles (EVs) from conditioned media of differentiated TM cells in culture isolated from non-glaucomatous and glaucomatous human donor eyes. Methods EVs were purified using the double cushion ultracentrifugation gradient method. Fractions containing EV markers CD9 and TSG101 were analyzed using nanoparticle tracking analysis to determine their size and concentration. We then determined their proteomic cargo by mass spectrometry and compared protein profiles of EVs between normal and glaucomatous TM cells using PANTHER. Key protein components from EV preparations were validated with Western blotting. Results Results showed changes in the percentage of ECM proteins associated with EVs from glaucomatous TM cells compared to non-glaucomatous TM cells (5.7% vs 13.1% respectively). Correspondingly, we found that two ECM-related cargo proteins found across all samples, fibronectin and EDIL3 were significantly less abundant in glaucomatous EVs (&lt;0.3 fold change across all groups) compared to non-glaucomatous EVs. Discussion Overall, these data establish that ECM materials are prominent proteomic cargo in EVs from TM cells, and their binding to EVs is diminished in glaucoma.","PeriodicalId":73096,"journal":{"name":"Frontiers in ophthalmology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134944284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0