Investigative ophthalmology & visual science最新文献

{"title":"Systemic Hypoxia Increases Retinal Blood Flow but Reduces the Oxygen Saturation Less in Peripheral Than in Macular Vessels in Normal Persons.","authors":"Jacob Drachmann, Line Petersen, Signe Krejberg Jeppesen, Toke Bek","doi":"10.1167/iovs.66.6.43","DOIUrl":"10.1167/iovs.66.6.43","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal vascular diseases are characterized by regional differences in the distribution of morphological lesions that may be related to regional differences in the autoregulation of retinal blood flow. The purpose of the present study was to investigate how systemic hypoxia affects blood flow and oxygen saturation in different vascular areas in normal persons.</p><p><strong>Methods: </strong>In 28 normal persons, oxygen saturation and vessel diameters were measured by dual wavelength retinal oximetry, and blood flow velocity by Doppler OCT in the peripapillary arterioles supplying and venules draining the four retinal quadrants, and in an arteriolar and a venular branch from the upper temporal arcade towards respectively the retinal periphery and the macular area. The measurements were performed during normoxia and during breathing of a gas mixture containing 12.5% oxygen.</p><p><strong>Results: </strong>Systemic hypoxia reduced the oxygen saturation in peripapillary arterioles by approximately 11% (P < 0.001) and increased the peripapillary blood flow by approximately 40% (P < 0.001). Systemic hypoxia also reduced the oxygen saturation in the macular arterioles and venules and in the peripheral arterioles (P < 0.003), but not in the peripheral venules (P = 95). The blood flow increased significantly in both macular and peripheral arterioles and venules (P < 0.04).</p><p><strong>Conclusions: </strong>Systemic hypoxia can affect the venous oxygen saturation in vessels draining the retinal periphery and the macular area differently. The findings may help to understand the regionally varying manifestations of retinal vascular disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284394","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}

{"title":"Corneal Sensory Denervation Causes Epithelial Ferroptosis and Delayed Healing in Mice.","authors":"Ning Wang, Yizhou Li, Xiaolei Wang, Lingling Yang, Jing Zhang, Jun Cheng, Xiaoyue Jiang, Xia Qi, Chao Wei, Qingjun Zhou, Ya Li, Suxia Li","doi":"10.1167/iovs.66.6.28","DOIUrl":"10.1167/iovs.66.6.28","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the role and mechanism of corneal nerves in regulating epithelial cell response against ferroptosis.</p><p><strong>Methods: </strong>Denervated mouse models were established via surgical axotomy and capsaicin treatment. Monochlorobimane staining was employed to detect cellular glutathione (GSH) levels in the corneal epithelium, and real-time quantitative PCR and immunofluorescence staining were used to evaluate GSH-related gene expression in denervated models and corneas of patients with neurotrophic keratitis. Scanning electron microscopy was utilized to observe mitochondrial morphology in corneal epithelial cells. Ferroptosis inhibitor ferrostatin-1 was administered post-corneal scrape in capsaicin-treated mice, followed by transcriptomic sequencing. The p53 agonist Kevetrin activated p53 in scraped corneas and cultured corneal epithelial cells. Furthermore, capsaicin was topically applied to Trp53+/- mice, followed by corneal epithelial scraping.</p><p><strong>Results: </strong>In denervated models, the expression of GSH-related genes was downregulated, and mitochondrial morphology exhibited characteristics of ferroptosis in corneal epithelial cells. The delay in corneal wound healing induced by TRPV1+ sensory denervation was ameliorated by ferrostatin-1 treatment. RNA sequencing and immunofluorescence staining demonstrated upregulated p53 in TRPV1-denervated mice, which was subsequently downregulated following ferrostatin-1 treatment. Kevetrin exacerbated wound healing delays, whereas Trp53+/- mice exhibited accelerated healing post-capsaicin denervation compared to wild-type controls.</p><p><strong>Conclusions: </strong>TRPV1+ sensory nerves play a regulatory role in preventing ferroptosis of corneal epithelial cells through the p53/AKT/mTOR signaling pathway. Targeting this pathway may offer therapeutic potential for neurotrophic keratopathy and related disorders.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247914","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}

{"title":"Does the Association Between Eye Disease and Cognitive Function Vary by Genetic Risk of Cognitive Decline? An Analysis of Hospital Data With Replication in the Canadian Longitudinal Study on Aging.","authors":"Emily Tran, Mohan Rakesh, Gisele Li, Ellen E Freeman, Marie-Hélène Roy-Gagnon","doi":"10.1167/iovs.66.6.71","DOIUrl":"10.1167/iovs.66.6.71","url":null,"abstract":"<p><strong>Purpose: </strong>Age-related eye diseases are inconsistently associated with cognitive decline which could be due to effect modification. The purpose of this study was to investigate whether two genetic factors previously found to be associated with cognitive decline, the KIBRA (WWC1) and PDE7A/MTFR1 genes, modify the association between eye disease and cognitive function.</p><p><strong>Methods: </strong>Data from a Montreal hospital-based cross-sectional study (n = 302) were used for the primary analysis. Candidate single-nucleotide polymorphisms (SNPs) rs17070145 (KIBRA gene) and rs10808746 (PDE7A/MTFR1 gene) were included in linear regression models to test for effect modification of the relationship between eye disease (glaucoma or age-related macular degeneration [AMD]) and cognitive function. Six oral cognitive tests were used. A replication analysis was done using the Quebec data from the Canadian Longitudinal Study on Aging (CLSA) (n = 4238). Effect modifications by expanded genomic regions around the candidate SNPs were tested.</p><p><strong>Results: </strong>Three statistically significant interactions with two cognitive function measures -category verbal fluency and immediate story recall-were found in the Montreal study: glaucoma and AMD with rs17070145 and verbal fluency (P < 0.03) and glaucoma with rs10808746 with immediate story recall (P < 0.05). Similar interactions, although not with the same cognitive measure, were found in the CLSA: AMD with KIBRA and glaucoma with PDE7A/MTFR1.</p><p><strong>Conclusions: </strong>Our results suggest that the KIBRA and PDE7A/MTFR1 genes may modify the association between eye disease and cognitive function. This knowledge may help to better understand the mechanism by which glaucoma and AMD are related to cognitive function.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"71"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475164","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}

{"title":"Three-Dimensional Culture of Orbital Fibroblasts From Thyroid Eye Disease Induce In Vivo-Like Tissue Remodeling and Fibrosis.","authors":"Xiaoli Bao, Zhihui Xu, Xi Wang, Te Zhang, Huijing Ye, Huasheng Yang","doi":"10.1167/iovs.66.6.67","DOIUrl":"10.1167/iovs.66.6.67","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the characteristics and molecular mechanisms of orbital fibroblasts under three-dimensional (3D)-culture conditions.</p><p><strong>Methods: </strong>Orbital connective tissue was collected from patients with thyroid eye disease (TED) and normal controls. Primary fibroblasts were cultured and used to generate 3D microspheres via the hanging drop. These spheroids were cultured for nine days, followed by biomechanical testing, transmission electron microscopy (TEM), and RNA sequencing for transcriptomic analysis. Multiplex immunofluorescence staining was used to assess fibrosis markers, and quantitative PCR validated gene expression changes. TED and normal control (NC) tissues, as well as primary cultured fibroblasts, were also subjected to transcriptomic sequencing.</p><p><strong>Results: </strong>TED-3D microspheres exhibited enhanced contractility, denser fiber deposition, and a characteristic fibrous ring at the periphery. TEM revealed more extracellular matrix (ECM) deposition and stronger tissue remodeling in TED-3D. Fibrosis markers (α-SMA, COL1A1, FN1) increased significantly in TED-3D. Biomechanical testing showed higher stiffness in TED-3D compared to NC-3D. Transcriptomic analysis revealed significant differences, with genes involved in ECM remodeling and fibrosis pathways enriched in TED-3D. Transcriptomic comparison of TED-tissue, TED-2D, and TED-3D revealed that TED-3D is closer to tissue than TED-2D.</p><p><strong>Conclusions: </strong>The 3D culture of orbital fibroblasts from TED induces in vivo-like tissue remodeling and fibrosis features. Compared to traditional two-dimensional culture, the expression pattern of TED-3D is closer to tissue, making it a more effective model for studying the mechanisms of TED-related fibrosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"67"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475198","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}

{"title":"RAGE Is Essential for Subretinal Fibrosis in Laser-Induced Choroidal Neovascularization: Therapeutic Implications.","authors":"Parameswaran G Sreekumar, Mi-Hyun Nam, Elise Hong, Ram Kannan, Ram H Nagaraj","doi":"10.1167/iovs.66.6.30","DOIUrl":"10.1167/iovs.66.6.30","url":null,"abstract":"<p><strong>Purpose: </strong>Subretinal fibrosis, a complication of neovascular age-related macular degeneration (nAMD), involves the epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells as a contributing mechanism. The receptor for advanced glycation end products (RAGE) is a multiligand receptor implicated in fibrotic diseases, but its role in subretinal fibrosis has not been studied. This study investigated the role of RAGE in subretinal fibrosis.</p><p><strong>Methods: </strong>Subretinal fibrosis was induced in male RAGE-/- and wild-type (WT) mice via laser photocoagulation, and fibrosis lesion volume was assessed on day 35 using optical coherence tomography and immunostaining. In vitro, EMT was induced in primary human RPE cells with transforming growth factor-beta 2 (TGF-β2). The role of RAGE in EMT was studied in cells pretreated with RAGE antagonists (FPS-ZM1 or azeliragon), followed by cotreatment with TGF-β2 for 48 hours. Signaling studies were conducted by pretreatment with FPS-ZM1 for 2 hours, cotreatment with TGF-β2 for 60 minutes, and subsequent immunoblot analysis.</p><p><strong>Results: </strong>In RAGE-/- mice, subretinal fibrosis after laser-induced choroidal neovascularization was significantly reduced, with a smaller fibrosis volume, less inflammation, decreased activation of pSmad2, and reduced deposition of fibrotic markers (αSMA, collagen I) compared to WT mice. In vitro treatment with TGF-β2 in human RPE cells increased mitochondrial reactive oxygen species and upregulated EMT markers (αSMA, collagen I, and fibronectin), which were inhibited by cotreatment with FPS-ZM1 or azeliragon. FPS-ZM1 blocked TGF-β2-induced Smad2-dependent signaling and EMT without affecting the extracellular signal-regulated kinase (ERK) pathway.</p><p><strong>Conclusions: </strong>Our findings indicate that RAGE plays a role in RPE cell EMT in subretinal fibrosis and that RAGE antagonists attenuate this process, making RAGE a promising therapeutic target for subretinal fibrosis in nAMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"30"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247917","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}

{"title":"Studies of All-trans Retinoic Acid Transport in the Eye.","authors":"Saptarshi Chatterjee, Ankana Roy, Jianshi Yu, Arthur Thomas Read, Melissa R Bentley-Ford, Machelle T Pardue, Maureen A Kane, M G Finn, C Ross Ethier","doi":"10.1167/iovs.66.6.84","DOIUrl":"10.1167/iovs.66.6.84","url":null,"abstract":"<p><strong>Purpose: </strong>Myopia incidence is increasing globally. All-trans retinoic acid (atRA) is important in myopigenic retinoscleral signaling, motivating research on its ocular transport. However, atRA's weak autofluorescence limits its direct visualization in tissues. Further, atRA is hydrophobic and must bind to protein carriers for transport. We assessed a fluorescent analog of atRA (LightOx 14, CAS:198696-03-6, referred as \"floRA\"), as an experimentally accessible atRA surrogate by: (i) evaluating its binding to carrier proteins and (ii) visualizing its distribution in ocular tissues.</p><p><strong>Methods: </strong>Binding: We assessed atRA-carrier protein binding using fluorescence quenching assays with bovine serum albumin (BSA), high density lipoprotein (HDL), apolipoprotein A-I (Apo A-I), and retinol binding protein 4 (RBP4). Direct visualization: Wild-type C57BL/6J mice were euthanized, their eyes were enucleated, and wedges containing sclera and choroid were incubated for specific durations in 50 µM floRA + BSA. The wedge centers were cryo-sectioned and counterstained for nuclei. Fluorescent micrographs were acquired and analyzed using ImageJ software.</p><p><strong>Results: </strong>Association constants (Ka) for atRA and floRA binding to carrier proteins were similar and ranged from 2 to 13 × 105 M-1, indicating nonspecific binding. floRA could be visualized in the sclera and choroid, yet showed significant spatial heterogeneity (enhanced fluorescence often colocalizing with nuclei).</p><p><strong>Conclusions: </strong>floRA is a reasonable surrogate for atRA binding to BSA, HDL, Apo A-I, and RBP4. Considering these proteins' relative serum and extravascular abundances, and their similar binding affinity to atRA, we predict that serum albumin is an important atRA carrier. Use of floRA in whole tissue tracer studies shows promise but requires further refinement.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"84"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12212452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528011","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}

{"title":"Erratum in: Ferroptosis Contributes to Retinal Ganglion Cell Loss in GLAST Knockout Mouse Model of Normal Tension Glaucoma.","authors":"","doi":"10.1167/iovs.66.6.44","DOIUrl":"10.1167/iovs.66.6.44","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"44"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284393","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}

{"title":"Pyroptosis Mediated by ROS/Caspase-3/GSDME Pathway in Aspergillus fumigatus-Induced Fungal Keratitis.","authors":"Jingze Kan, Shiqi Song, Mengzhu Liu, Qiang Xu, Jieun Lee, Jintao Sun, Shasha Xue, Xiaoyan Sun, Chengye Che","doi":"10.1167/iovs.66.6.52","DOIUrl":"10.1167/iovs.66.6.52","url":null,"abstract":"<p><strong>Purpose: </strong>Gasdermin E (GSDME), cleaved by (casp-3) activation, is known as a key executor in pyroptosis. However, its role in fungal keratitis (FK) remains unclear. Thus we analyzed the role of GSDME, as well as its signaling pathway in Aspergillus fumigatus (AF)-induced FK.</p><p><strong>Methods: </strong>We conducted experiments using a mouse model and human corneal epithelial cells. Initially, we infected mice with AF at various time intervals and examined the progression of FK lesions, selecting the time point with the most severe lesions. Next, we pre-treated the subjects with various cytokine inhibitors that may influence pyroptosis. We then assessed the development of FK lesions and the production of inflammatory cytokines using qRT-PCR, flow cytometry, transmission electron microscopy, as well as Western blotting.</p><p><strong>Results: </strong>The optimal stimulation time for corneal epithelial cells in mice and humans was determined to be three days and 12 hours, respectively. In both the mouse and corneal epithelial cell models, GSDME significantly mediated AF-induced pyroptosis downstream of the reactive oxygen species (ROS)/casp-3/GSDME pathway and greatly influenced the inflammatory process and keratitis in AF-induced FK.</p><p><strong>Conclusions: </strong>Overall, GSDME played a crucial role in pyroptosis during corneal inflammation. By modulating IL-1β release during pyroptosis, GSDME had a significant impact on the host immune response in FK. This process could be inhibited by blocking the ROS/casp-3/GSDME pathway, potentially offering a novel treatment option for reducing corneal opacity in FK.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"52"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316931","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}

{"title":"Letter to the Editor: \"VEP Latency Delay Reflects Demyelination Beyond the Optic Nerve in the Cuprizone Model\".","authors":"Henrique Rocha Mendonça, Ana Carolina de Pádua, Saulo Augusto Alves da Cruz, Greice Nascimento Pires, Sheila Espírito-Santo","doi":"10.1167/iovs.66.6.27","DOIUrl":"10.1167/iovs.66.6.27","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247916","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}

{"title":"Anti-VEGF Agents Clearance Through the Aqueous Outflow Pathway in a Rat Model.","authors":"Assaf Ben-Arzi, Itay Spector, Yariv Keshet, Orly Gal-Or, Irit Bahar, Assaf Dotan","doi":"10.1167/iovs.66.6.1","DOIUrl":"10.1167/iovs.66.6.1","url":null,"abstract":"<p><strong>Purpose: </strong>Sustained increase in intraocular pressure (IOP) following intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in the treatment of retinal disease has been theoretically attributed to aggregation of anti-VEGF in the iridocorneal angle. However, previous studies by our group showed full clearance of intravitreally injected bevacizumab, aflibercept, and ranibizumab. The objective of this study was to further analyze and compare the clearance of these anti-VEGF agents from the eye after a single injection in a rat model.</p><p><strong>Methods: </strong>Brown Norway rats received an intravitreal injection of 3 µl anti-VEGF at the standard concentration 3 days following induction of choroidal neovascularization. The eyes were processed at 0, 3, 6, 24, and 48 hours thereafter, and immunofluorescence was evaluated with confocal microscopy and 3D reconstruction analysis. The signal concentration was calculated, and the drug clearance rate was measured. The immunohistochemistry process was validated with negative and positive control groups.</p><p><strong>Results: </strong>The immunofluorescent signal was positive for all anti-VEGF agents at the trabecular meshwork, Schlemm's canal, and episcleral veins. Anti-VEGF immunostaining peaked immediately after injection and then decreased gradually to negligible at 48 hours (P < 0.05). All three agents demonstrated an identical pattern (P > 0.05). The clearance rate of anti-VEGF from the iridocorneal angle ranged between 98.68% and 99.87% at 48 hours.</p><p><strong>Conclusions: </strong>Bevacizumab, aflibercept, and ranibizumab cleared completely from the iridocorneal angle at 48 hours in the brown Norway rats following a single intravitreal injection and with similar a clearance rate. These findings support our earlier studies refuting the anti-VEGF aggregation hypothesis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199149","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}