Investigative ophthalmology & visual science最新文献

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Exploring the Interplay Between Hyperthermia and Cytotoxic Drugs in Ocular Melanoma Cell Lines: Implications and Variability in Treatment Efficiency. 探讨热疗和细胞毒性药物在眼部黑色素瘤细胞系中的相互作用:治疗效率的意义和可变性。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.71
Pascal-Raphael Blersch, Torsten Hoyer, Christoph Alexiou, Ludwig M Heindl, Antoniu-Oreste Gostian, Stefan Lyer
{"title":"Exploring the Interplay Between Hyperthermia and Cytotoxic Drugs in Ocular Melanoma Cell Lines: Implications and Variability in Treatment Efficiency.","authors":"Pascal-Raphael Blersch, Torsten Hoyer, Christoph Alexiou, Ludwig M Heindl, Antoniu-Oreste Gostian, Stefan Lyer","doi":"10.1167/iovs.66.12.71","DOIUrl":"10.1167/iovs.66.12.71","url":null,"abstract":"<p><strong>Purpose: </strong>Uveal and conjunctival melanomas are rare ocular malignancies that present significant diagnostic and therapeutic challenges. This study investigates the efficacy of combining hyperthermic treatments with chemotherapeutics, such as cisplatin, docetaxel, and mitoxantrone, to develop more effective therapies for specific melanoma subtypes, aiming to overcome the limitations of traditional approaches.</p><p><strong>Methods: </strong>The study used hyperthermia by exposing melanoma cell lines to temperatures of 42°C, 45°C, and 47°C for 1 hour. Alongside hyperthermia, cytotoxic drugs were applied at different concentrations to assess their combined effects on cell proliferation and viability. Expression of heat shock proteins was evaluated by immunocytochemistry stainings and Western blots.</p><p><strong>Results: </strong>Findings reveal that certain melanoma cell lines exhibited increased proliferation at 42°C without a significant decrease in cell confluence. Conversely, temperatures of 45°C and above significantly impaired cell viability. Comparative statistical analysis suggests synergistic effects when combining mild to elevated hyperthermia with cisplatin and mitoxantrone, and to some extent with docetaxel.</p><p><strong>Conclusions: </strong>This study serves as preliminary work for the inclusion of superparamagnetic iron oxide nanoparticles functionalized with cytotoxic drugs, which may present a promising therapeutic strategy for treating ocular melanomas. Although further research is necessary, this approach has the potential to significantly advance the treatment landscape for these ocular malignancies, offering a targeted, effective, and minimally invasive option for patients.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"71"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Role of Copper Transporter CTR1 and Therapeutic Potential of Copper Chelators in Retinal Ischemia-Reperfusion Injury. 铜转运体CTR1在视网膜缺血再灌注损伤中的新作用及铜螯合剂的治疗潜力。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.70
Mai Yamamoto, Dipankar Ash, Varadarajan Sudhahar, Syed Adeel H Zaidi, Modesto A Rojas, Zhimin Xu, Stephanie Kelley Spears, Ruth B Caldwell, Tohru Fukai, Masuko Ushio-Fukai
{"title":"Novel Role of Copper Transporter CTR1 and Therapeutic Potential of Copper Chelators in Retinal Ischemia-Reperfusion Injury.","authors":"Mai Yamamoto, Dipankar Ash, Varadarajan Sudhahar, Syed Adeel H Zaidi, Modesto A Rojas, Zhimin Xu, Stephanie Kelley Spears, Ruth B Caldwell, Tohru Fukai, Masuko Ushio-Fukai","doi":"10.1167/iovs.66.12.70","DOIUrl":"10.1167/iovs.66.12.70","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ischemia contributes to vision loss in ischemic and diabetic retinopathies through oxidative stress, neurovascular injury, and inflammation. Copper (Cu), whereas an essential micronutrient, can be toxic in excess and is regulated by Cu transporters such as CTR1. However, the role of CTR1 in ischemic retinopathy remains unclear.</p><p><strong>Methods and results: </strong>Retinal ischemia-reperfusion (IR) injury was induced by elevating intraocular pressure (IOP) to 110 millimeters of mercury (mm Hg) for 40 minutes in the right eyes of Ctr1 heterozygous (Ctr1+/-) and wild-type (WT) mice. In WT mice, IR triggered rapid CTR1 upregulation and increased retinal Cu levels (measured by inductively coupled plasma mass spectrometry [ICP-MS]). IR injury caused retinal ganglion cell (RGC) loss, inner retinal thinning, vascular degeneration, and apoptosis, all of which were significantly attenuated in Ctr1+/- mice. Ctr1+/- mice also exhibited reduced microglial (Iba1⁺) and glial cells (GFAP⁺) activation and preserved visual function, as assessed by electroretinography. Mechanistically, IR-induced reactive oxygen species (({{rm{O}}_{2}}^{-})) production (DHE staining), upregulation of NADPH oxidase components (NOX2 and p47phox), and NF-κB activation were markedly suppressed in Ctr1+/- mice. Treatment with the Cu chelator tetrathiomolybdate (TTM) similarly reduced retinal thinning, neurovascular damage, apoptosis, gliosis, and oxidative stress after IR injury.</p><p><strong>Conclusions: </strong>CTR1 plays a central role in mediating Cu-dependent oxidative stress, neurovascular degeneration, and inflammation following retinal IR injury. Targeting the CTR1-Cu axis may represent a novel therapeutic strategy for ischemic retinopathy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"70"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Temporal Sensitivity Under Photopic and Scotopic Conditions Across the Cortical Visual Hierarchy. 光暗条件下皮层视觉层次的时间敏感性。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.12
Deena Elul, Ayelet McKyton, Netta Levin
{"title":"Temporal Sensitivity Under Photopic and Scotopic Conditions Across the Cortical Visual Hierarchy.","authors":"Deena Elul, Ayelet McKyton, Netta Levin","doi":"10.1167/iovs.66.12.12","DOIUrl":"10.1167/iovs.66.12.12","url":null,"abstract":"<p><strong>Purpose: </strong>Behavioral and electrophysiological studies have shown that vision is slower under scotopic conditions (dark, activating only rods) than photopic conditions (light, activating only cones). However, slower scotopic processing cannot be solely explained by findings that rod signals are slower than cone signals, and it is unknown whether temporal processing differences persist in cortex. Flickering stimuli have previously been used in functional MRI (fMRI) studies to probe photopic cortical temporal sensitivity. This fMRI study investigates flicker sensitivity under photopic and scotopic conditions across the cortical visual hierarchy.</p><p><strong>Methods: </strong>Fourteen participants viewed a stimulus flickering at six frequencies (2-10 Hz) under photopic and scotopic conditions during fMRI scanning. Retinotopic and high-level visual areas were delineated for each subject with population receptive field modeling (using a drifting bar) and a functional localizer (using images of objects).</p><p><strong>Results: </strong>In most areas, higher mean activation was observed under photopic than under scotopic conditions. However, peak activation was higher only in V1 and ventral retinotopic areas. The pattern of change over frequencies differed between lighting conditions in retinotopic areas, but not in most high-level areas. Under scotopic conditions, the largest BOLD response was observed at low frequencies throughout visual cortex. Under photopic conditions, BOLD responses appeared largely unchanging across frequencies, with a trend towards preferring higher frequencies in V1.</p><p><strong>Conclusions: </strong>Selectivity for lower frequencies under scotopic conditions was observed throughout visual cortex, in contrast to limited selectivity under photopic conditions. This low-frequency preference could allow more time for extracting information from sparse scotopic stimuli.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"12"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12416517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ocular and Systemic Risk Factors and Biomarkers for Primary Glaucoma: An Umbrella Review of Systematic Reviews With Meta-Analyses. 原发性青光眼的眼部和全身危险因素和生物标志物:综合系统评价和荟萃分析。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.35
Ru Yue Shen, Yuqiao Zhang, Li Jia Chen, Carol Y Cheung, Yuanbo Liang, Clement C Tham, Poemen P Chan
{"title":"Ocular and Systemic Risk Factors and Biomarkers for Primary Glaucoma: An Umbrella Review of Systematic Reviews With Meta-Analyses.","authors":"Ru Yue Shen, Yuqiao Zhang, Li Jia Chen, Carol Y Cheung, Yuanbo Liang, Clement C Tham, Poemen P Chan","doi":"10.1167/iovs.66.12.35","DOIUrl":"10.1167/iovs.66.12.35","url":null,"abstract":"<p><strong>Purpose: </strong>To synthesize and evaluate the quality of evidence from existing meta-analyses on ocular and systemic factors and biomarkers associated with primary glaucoma.</p><p><strong>Methods: </strong>Systematic reviews with meta-analysis evaluating ocular and systemic factors or biomarkers of glaucoma were included. Searches of PubMed, Embase, and Cochrane Library were conducted from inception to June 25, 2023, without language restrictions. Two researchers independently conducted screening, data extraction, and quality appraisal. The summary effect size, 95% confidence interval, and 95% prediction interval were estimated by random-effect models. The between-study heterogeneity (I2), evidence of small-study effects, and evidence of excess significance bias were reported. The equivalent standardized mean differences or odds ratios were calculated from original study estimates.</p><p><strong>Results: </strong>Thirty-six systematic reviews and meta-analyses were included, examining 87 factors related to ocular biometrics, lifestyle habits, diets, ocular and systemic disorders, and biomarkers from ocular imaging, serum, plasma, and aqueous humor. Three ocular factors (intraocular pressure, myopia, and corneal hysteresis) and one peripheral biomarker (total antioxidant status) were graded as highly suggestive evidence. Among the 41 factors, 8 (20%) were classified as suggestive evidence, while 3 (7%) of the 46 biomarkers received the same classification. Additionally, 29 of 54 (54%) factors and 18 of 33 (55%) biomarkers were graded as weak evidence.</p><p><strong>Conclusions: </strong>This umbrella review highlights the evidence hierarchy of various ocular and systemic risk factors and biomarkers associated with glaucoma. Further high-quality studies are essential to strengthen the evidence base.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"35"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Absence of Glaucoma in Tg-MYOCY437H Mice of Diverse Genetic Backgrounds. 不同遗传背景的Tg-MYOCY437H小鼠青光眼不存在
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.40
Nicholas G Tolman, Marina Simón, Felicia A Juarez, Chi Zhang, Zhivka I Hristova, Tionna B Ouellette, Michael A Sellarole, Wilhelmine N deVries, Christa Montgomery, Simon W M John
{"title":"Absence of Glaucoma in Tg-MYOCY437H Mice of Diverse Genetic Backgrounds.","authors":"Nicholas G Tolman, Marina Simón, Felicia A Juarez, Chi Zhang, Zhivka I Hristova, Tionna B Ouellette, Michael A Sellarole, Wilhelmine N deVries, Christa Montgomery, Simon W M John","doi":"10.1167/iovs.66.12.40","DOIUrl":"10.1167/iovs.66.12.40","url":null,"abstract":"<p><strong>Purpose: </strong>Mutations in the myocilin (MYOC) gene cause elevated intraocular pressure and glaucoma. To better understand the factors influencing susceptibility to glaucoma, we studied the MYOC mutation (MYOCY437H).</p><p><strong>Methods: </strong>We characterized ocular phenotypes in Tg-MYOCY437H mice on nine different mouse strain backgrounds.</p><p><strong>Results: </strong>No glaucoma-related phenotypes were observed. We detected neither elevated intraocular pressure (daytime readings) nor optic nerve degeneration differences between wild type (WT) and Tg-MYOCY437H mice. This included an absence of Tg-MYOCY437H-induced phenotypes on a mixed B6SJL background that best reflected the original publications with this strain. We confirmed that this result was not due to an absence of transgene expression in ocular tissues.</p><p><strong>Conclusions: </strong>Our data indicate undefined complexity and that the previously reported glaucoma phenotypes are not robust across all institutions and environments.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"40"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systemic and Local Lipids in Nonhuman Primates With Drusen and Age-Related Maculopathies. 患有德鲁森和年龄相关黄斑病变的非人灵长类动物的全身和局部脂质。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.41
Carol Villafuerte-Trisolini, Sophie M Le, Tzu-Ni Sin, Leon Huynh, Megan Gong, Tony Shen, Jaewon Heo, Karolina Roszak, Ana Santos Raposo, James Graham, Peter Havel, Kevin Choy, Sina Farsiu, Sara M Thomasy, Glenn Yiu
{"title":"Systemic and Local Lipids in Nonhuman Primates With Drusen and Age-Related Maculopathies.","authors":"Carol Villafuerte-Trisolini, Sophie M Le, Tzu-Ni Sin, Leon Huynh, Megan Gong, Tony Shen, Jaewon Heo, Karolina Roszak, Ana Santos Raposo, James Graham, Peter Havel, Kevin Choy, Sina Farsiu, Sara M Thomasy, Glenn Yiu","doi":"10.1167/iovs.66.12.41","DOIUrl":"10.1167/iovs.66.12.41","url":null,"abstract":"<p><strong>Purpose: </strong>Lipids are a principal component of drusen and are involved in the pathobiology of age-related macular degeneration (AMD). Nonhuman primates (NHPs) develop macular drusen and may provide insight into circulating or local lipids in AMD.</p><p><strong>Methods: </strong>We evaluated aged rhesus macaques by fundus photography, optical coherence tomography (OCT), and fundus autofluorescence, as well as measured fasting plasma glucose, total cholesterol, high- and low-density lipoproteins, triglycerides, and apolipoprotein (Apo) A1, B, CIII, and E. Retinal tissues were collected for electron microscopy and immunostained for oil red O, ApoE, and ApoB.</p><p><strong>Results: </strong>Among 203 adult macaques (mean age 19.1 ± 3.1 years), 25 animals (12.1%) exhibited soft drusen with sub-RPE deposits, while 59 (28.6%) had yellow punctate dots that were mostly hyperautofluorescent without RPE elevation on OCT. Drusen prevalence increased with older age (P = 0.001) but not with plasma lipids (P > 0.05 for all), while the punctate dot phenotype was associated with older age (P = 0.014), higher fasting glucose (P = 0.023), low-density lipoprotein cholesterol (P = 0.022), and ApoB (P = 0.017). Ultrastructure revealed NHP drusen consisting of extracellular sub-RPE lipid particles, whereas punctate dots appeared to correspond to individual RPE cells with intracellular lipid vacuoles. Both sub-RPE and intra-RPE lipids of the two phenotypes contained neutral lipids and ApoE, while ApoE and ApoB appeared to be expressed in RPE.</p><p><strong>Conclusions: </strong>In rhesus macaques, soft drusen are extracellular lipid deposits associated with older age, while punctate dots are intracellular lipids linked to age, hyperglycemia, and hyperlipidemia, suggesting differential dysregulation of lipid transport in these NHP models of AMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"41"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability. Zeb1通过维持上皮再生促进氮芥诱导的角膜上皮伤口愈合。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.33
Fuhua Wang, Xiaolei Sun, Yanling Dong, Fang Cheng, Jiangli Fan, Xiaoqin Lu, Douglas Emery, Hui Shao, Wei Wang, Lijun Zhang, Douglas C Dean, Yongqing Liu
{"title":"Zeb1 Facilitates Nitrogen Mustard-Induced Corneal Epithelial Wound Healing by Maintaining Epithelial Renewability.","authors":"Fuhua Wang, Xiaolei Sun, Yanling Dong, Fang Cheng, Jiangli Fan, Xiaoqin Lu, Douglas Emery, Hui Shao, Wei Wang, Lijun Zhang, Douglas C Dean, Yongqing Liu","doi":"10.1167/iovs.66.12.33","DOIUrl":"10.1167/iovs.66.12.33","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize Zeb1 regulation of nitrogen mustard (NM)-induced acute corneal epithelial damage and its recovery in mice.</p><p><strong>Methods: </strong>This study utilized topical fluorescein staining and section immunohistochemistry to evaluate NM-induced acute corneal epithelial damage and its recovery in both Zeb1 wild-type and heterozygous knockout mice, as well as real-time quantitative PCR and chromatin immunoprecipitation to delineate the mechanism underlying Zeb1 regulation of such corneal epithelial damage and recovery.</p><p><strong>Results: </strong>Topical application of NM on the central cornea causes an immediate reduction of Zeb1 expression, followed by de-epithelization and epithelial cell death, along with cell proliferation resulting in epithelial recovery. Monoallelic knockout of Zeb1 decreased NM-induced acute epithelial damage but delayed the recovery from the damage.</p><p><strong>Conclusions: </strong>Zeb1 facilitates NM-induced corneal epithelial wound healing by maintaining epithelial renewability and thus is a potential therapeutic target to reduce acute mustard gas keratopathy in early ocular pathogenesis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"33"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Connexin 36 Gap Junctions in Retinal Ganglion Cell Death After Corneal Alkali Burns. 连接蛋白36在角膜碱烧伤后视网膜神经节细胞死亡中的作用。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.43
ChunTing Qiu, Ting Zhang, Qin Wang, Kangyi Yang, Chunghim So, Feng Pan
{"title":"The Role of Connexin 36 Gap Junctions in Retinal Ganglion Cell Death After Corneal Alkali Burns.","authors":"ChunTing Qiu, Ting Zhang, Qin Wang, Kangyi Yang, Chunghim So, Feng Pan","doi":"10.1167/iovs.66.12.43","DOIUrl":"10.1167/iovs.66.12.43","url":null,"abstract":"<p><strong>Purpose: </strong>A corneal alkali burn can cause irreversible damage to both the cornea and retina. This study aims to investigate the role of the gap junction subunit connexin 36 (Cx36) in mediating secondary cell death and its impact on the apoptosis of retinal ganglion cells (RGCs) following ocular alkali burns, contributing to irreversible vision loss.</p><p><strong>Methods: </strong>Corneal alkali burn models were established in C57BL/6J and Cx36 knockout (KO) mice by applying 1 M sodium hydroxide to the cornea. The gap junction blocker meclofenamic acid (MFA; 200 µM) was administered via intravitreal injection immediately after the corneal alkali burn. Immunohistochemistry was used to assess RGC survival, whereas patch-clamp recording evaluated the RGC function.</p><p><strong>Results: </strong>In the mouse model, dysfunction and cell death in RGCs were observed within 6 hours following ocular alkali burns. Our results showed a time-dependent increase in RGC loss, peaking at 24 hours, with damage spreading from the peripheral to the central regions. The study revealed a significant reduction in light sensitivity and light-evoked excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs) in ON and OFF transient alpha RGCs after 6 hours of corneal alkali burns. The Cx36 knockout mice exhibited significantly increased RGC survival. The data suggests that MFA has a neuroprotective effect, preventing secondary RGC damage.</p><p><strong>Conclusions: </strong>Our findings indicate that Cx36 gap junctions mediate secondary cell death of RGCs following corneal alkali injuries and may serve as a potential target for neuroprotective therapy. The gap junction antagonist MFA, a US Food and Drug Administration (FDA)-approved drug, could prevent this secondary cell death, highlighting its potential as a therapeutic intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"43"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deep-Learning-Based Analysis of Disease-Specific Structural Biomarkers on Retinal Sensitivity in Neovascular Age-Related Macular Degeneration. 基于深度学习的疾病特异性结构生物标志物对新生血管性年龄相关性黄斑变性视网膜敏感性的分析
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-09-02 DOI: 10.1167/iovs.66.12.68
Gregor S Reiter, Klaudia Birner, Johannes Schrittwieser, Laetitia Hinterhuber, Irene Steiner, Markus Gumpinger, Simon Schürer-Waldheim, Hrvoje Bogunovic, Ursula Schmidt-Erfurth
{"title":"Deep-Learning-Based Analysis of Disease-Specific Structural Biomarkers on Retinal Sensitivity in Neovascular Age-Related Macular Degeneration.","authors":"Gregor S Reiter, Klaudia Birner, Johannes Schrittwieser, Laetitia Hinterhuber, Irene Steiner, Markus Gumpinger, Simon Schürer-Waldheim, Hrvoje Bogunovic, Ursula Schmidt-Erfurth","doi":"10.1167/iovs.66.12.68","DOIUrl":"10.1167/iovs.66.12.68","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the impact of disease-specific biomarkers on pointwise sensitivity (PWS) in patients with active neovascular age-related macular degeneration (nAMD) using two microperimetry (MP) instruments.</p><p><strong>Methods: </strong>Participants in this prospective cross-sectional study underwent imaging with a SPECTRALIS HRA+OCT and MP with the photopic MP-3 (NIDEK) and mesopic MAIA (CenterVue). Pigment epithelium detachment (PED), intraretinal and subretinal fluid (IRF, SRF), ellipsoid zone loss (EZL), and subretinal hyperreflective material (SHRM) were quantified using deep learning (DL). DL enabled co-registration between the MP and optical coherence tomography (OCT). Univariate and multivariable mixed-effects models using variable selection including interaction terms were used to assess the effects of the biomarkers on PWS.</p><p><strong>Results: </strong>Twenty eyes of 20 subjects (mean age, 76.0 years) were included. Sensitivity in the MAIA was lower (-2.87 dB; 95% confidence interval [CI], -3.15 to -2.59) than in the MP-3. Significant interactions between EZL and SRF, EZL and IRF, and between EZL and eccentricity were observed. EZL significantly reduced PWS (-1.30 dB; 95% CI, -2.08 to -0.51) at 0° eccentricity with SRF of 0.15 nL and absent IRF. IRF presence further decreased PWS by -2.57 dB (95% CI, -3.66 to -1.47). SRF negatively impacted PWS (-2.08 dB/nL; 95% CI, -2.53 to -1.64), but showed no association when EZL was present (+0.05 dB/nL; 95% CI, -0.81 to 0.92). SHRM presence and PED volume reduced PWS by -5.13 dB (95% CI, -5.83 to -4.43) and -0.71 dB/nL (95% CI, -0.92 to -0.50), respectively. Eccentricity only impaired function in the presence of EZL (-0.49 dB/°; 95% CI, -0.61 to -0.37).</p><p><strong>Conclusions: </strong>DL-quantified biomarkers mostly had a negative impact on PWS in nAMD, particularly IRF and SHRM presence. The above-mentioned biomarkers should be considered when managing patients with nAMD and using MP in trials and clinical settings.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"68"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of Optic Nerve Head Metrics and Parapapillary Gamma Zone With Myopia Onset and Progression in Children: The Hong Kong Children Eye Study. 视神经头和乳头旁伽玛区与儿童近视发生和发展的关系:香港儿童眼研究。
IF 4.7 2区 医学
Investigative ophthalmology & visual science Pub Date : 2025-08-01 DOI: 10.1167/iovs.66.11.1
Xiu Juan Zhang, Yi Li, Yuzhou Zhang, Xiaotong Li, Ka Wai Kam, Alvin L Young, Patrick Ip, Wei Zhang, Clement C Tham, Li Jia Chen, Jost B Jonas, Kyoko Ohno-Matsui, Chi Pui Pang, Jason C Yam
{"title":"Association of Optic Nerve Head Metrics and Parapapillary Gamma Zone With Myopia Onset and Progression in Children: The Hong Kong Children Eye Study.","authors":"Xiu Juan Zhang, Yi Li, Yuzhou Zhang, Xiaotong Li, Ka Wai Kam, Alvin L Young, Patrick Ip, Wei Zhang, Clement C Tham, Li Jia Chen, Jost B Jonas, Kyoko Ohno-Matsui, Chi Pui Pang, Jason C Yam","doi":"10.1167/iovs.66.11.1","DOIUrl":"10.1167/iovs.66.11.1","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the associations of optic nerve head (ONH) metrics and parapapillary gamma zone with myopia onset and progression in school children aged 6 to 8 years over a 3-year period.</p><p><strong>Methods: </strong>The ONH was imaged by spectral domain-optical coherence tomography (SD-OCT) using an adopted scan protocol comprising 24 equally spaced radial B-scans.</p><p><strong>Results: </strong>The study included 765 children (mean age = 7.69 ± 1.01 years, range = 6-8 years, refractive error = 0.33 ± 1.30 diopters [D] at baseline). Significant differences were found in disc ovality index, gamma zone area, Bruch's membrane opening distance (BMOD), temporal border tissue angle (BTA), and optic disc-fovea distance (DFD) across different refractive status groups (all P < 0.001). Multivariable logistic regression analysis indicated that female sex (odds ratio [OR] = 1.74, P = 0.006), longer axial length (OR = 1.81, P < 0.001), larger nasal BTA (OR = 1.01, P = 0.005), larger temporal BTA (OR = 1.01, P = 0.019), optic disc torsion (OR = 2.12, P = 0.007), and longer DFD at baseline (OR = 3.39, P < 0.001) were risk factors of myopia onset, whereas the presence of the gamma zone at baseline was not. In multivariable linear regression analysis, baseline disc ovality index, BMOD, nasal BTA, temporal BTA, and DFD, as well as changes in BMOD, nasal BTA, temporal BTA, gamma zone area, and DFD were significantly associated with spherical equivalent (SE) progression over 3 years.</p><p><strong>Conclusions: </strong>ONH parameters like nasal BTA, temporal BTA, disc torsion, and DFD may have predictive value for myopia onset and progression. As the myopic SE progresses, gamma zone enlargement coincides with the elongation of BMOD and DFD. It may be explained by an axial elongation-related Bruch's membrane opening shift into the temporal direction.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 11","pages":"1"},"PeriodicalIF":4.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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