Investigative ophthalmology & visual science最新文献

{"title":"Interactive Effects of IL-1β and TGF-β on Urokinase-Type Plasminogen Activator and α-Smooth Muscle Actin Expression by Corneal Fibroblasts.","authors":"Koji Sugioka, Teruo Nishida, Mai Yunoki, Noriko Mukai, Junko Murakami, Shunji Kusaka","doi":"10.1167/iovs.66.9.56","DOIUrl":"10.1167/iovs.66.9.56","url":null,"abstract":"<p><strong>Purpose: </strong>Corneal fibroblasts appear to differentiate into cells with opposing functions of collagen degradation and collagen synthesis in response to various stimuli during corneal wound healing process. Interleukin-1β (IL-1β) is a proinflammatory cytokine and promotes collagen degradation by corneal fibroblasts by upregulating their production of urokinase-type plasminogen activator (uPA). Transforming growth factor-β (TGF-β) induces the differentiation of corneal fibroblasts into myofibroblasts that express α-smooth muscle actin (α-SMA) and increase collagen synthesis, resulting in tissue contraction and remodeling. To investigate how these two factors might cooperatively regulate collagen metabolism during stromal wound healing, we investigated the potential interaction between IL-1β and TGF-β in the regulation of uPA and α-SMA expression by corneal fibroblasts.</p><p><strong>Methods: </strong>Human corneal fibroblasts were cultured in a three-dimensional gel of type I collagen. The uPA was detected by fibrin zymography and immunofluorescence staining, whereas α-SMA was detected by immunoblot analysis and immunofluorescence staining. Collagen gel contraction was assessed by measurement of gel diameter.</p><p><strong>Results: </strong>TGF-β not only downregulated uPA abundance in corneal fibroblasts under the basal condition, but also attenuated the upregulation of uPA expression by IL-1β. Conversely, IL-1β inhibited both the upregulation of α-SMA expression in these cells and the cell-mediated collagen gel contraction induced by TGF-β.</p><p><strong>Conclusions: </strong>Our results show that IL-1β and TGF-β interact to regulate the expression of uPA and α-SMA as well as collagen gel contraction mediated by corneal fibroblasts cultured in a collagen gel. They highlight the phase-dependent effects of cytokines and growth factors on collagen metabolism during corneal wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"56"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674800","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":"Inhibitor of DNA-Binding 3 Is a Novel Regulator of Limbal Epithelial Cell Migration Via the EphA2/Akt Signaling Pathway.","authors":"Elwin D Clutter, Wending Yang, Jacob Han, Nihal Kaplan, Han Peng","doi":"10.1167/iovs.66.9.2","DOIUrl":"10.1167/iovs.66.9.2","url":null,"abstract":"<p><strong>Purpose: </strong>Upon corneal injury, early and late transit amplifying (TA) cells, the progeny of epithelial stem cells, migrate to the site of the wound, which facilitates its closure. Understanding the targetable signals that guide such cell migration is essential for the development of novel wound-healing strategies.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was conducted in wild-type cornea. To investigate the role of inhibitor of DNA binding 3 (ID3) in the limbal epithelium, bulk RNA-seq was conducted in limbal epithelial cells with ID3 knockdown. hTCEpi cells were transfected with small interfering RNAs (siRNAs) against ID3, and cell migration was assessed using scratch wound assays.</p><p><strong>Results: </strong>The scRNA-seq revealed that ID3, a transcription factor, was preferentially expressed in the stem/early TA population of limbal epithelium. Bulk RNA-seq in limbal epithelial cells with ID3 knockdown suggested a role of ID3 in cell migration. Scratch wound assays confirmed that loss of ID3 in human limbal epithelial cells markedly accelerated wound sealing, indicating an inhibitory role of ID3 in cell migration. Gene Ontology analysis of the RNA-seq data suggested that ID3 negatively regulates EphA2 (a receptor tyrosine kinase) and Akt signaling, both of which have a critical role in cell migration. Consistently, loss of ID3 induced ligand-independent activation of EphA2, as well as enhanced phosphorylation of Akt proteins. Scratch wound assays demonstrated that both ligand-independent activation of EphA2 and phosphorylation of Akt were required for enhanced cell migration in cells lacking ID3.</p><p><strong>Conclusions: </strong>Our findings indicate that ID3, EphA2, and Akt form a novel signaling axis, which plays a critical role in corneal epithelial wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"2"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540233","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":"The Gut Microbial System Responds to Retinal Injury and Modulates the Outcomes by Regulating Innate Immune Activation.","authors":"Xuexue Cui, Caijiao Yi, Jian Liu, Jinyan Qi, Wen Deng, Xiangling Yuan, Ruiqi Zhou, Mei Chen, Qiang Xiang, Heping Xu","doi":"10.1167/iovs.66.9.6","DOIUrl":"10.1167/iovs.66.9.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to understand how the gut microbial system responds to retinal injury.</p><p><strong>Methods: </strong>Adult C57BL/6J mice were subjected to retinal laser burns or hypotony-induced retinal detachment (RD). One, 4, and 24 hours later, gut permeability (8 male mice and 8 female mice) was assessed using Evan's blue assay and the expression of ZO-1 in intestinal epithelial cells was examined by immunofluorescence. Circulating immune cells were evaluated by flow cytometry. The feces from control and lasered mice (n = 8) were collected under strict sterile conditions and processed for 16S DNA paired-end sequencing using the Illumina platform. The impact of gut dysbiosis on retinal wound healing was evaluated following treatment with Peros antibiotics (n = 8). Retinal pathologies were examined by immunohistochemistry.</p><p><strong>Results: </strong>Retinal laser injury significantly altered gut microbial profiles within 1 hour (β-diversity, multi-response permutation procedure [MRPP], P = 0.05). The abundance of Lignipirellula and Faecalibacterium was 100- and 6.67-fold lower, and the abundance of Akkermansia and Colidextribacter was 3.65- and 17.72-fold higher than non-lasered controls, respectively. Retinal laser burns and RD, not sham surgery, increased gut permeability at 1 hour and 4 hours by 3.82- and 24.76-fold, respectively, disrupted intestinal epithelial ZO-1 expression, accompanied by an increased population of circulating neutrophils and monocytes (P < 0.01) at 1 hour and 4 hours. Antibiotic treatment attenuated laser-/RD-induced gut permeability and the increased neutrophils and monocytes (in RD, P < 0.05). Antibiotic treatment also significantly reduced the severity of laser-induced choroidal neovascularization (CNV; P < 0.001) and RD-mediated photoreceptor apoptosis (P < 0.01), and suppressed Gr-1+ neutrophils (CNV, P < 0.001) and Iba-1+ cell infiltration (P < 0.001).</p><p><strong>Conclusions: </strong>A retina-gut axis exists. Retinal injury induces rapid gut microbial alteration, which in turn modulates innate immune cell activation and regulates the wound healing response.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540237","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":"Intravenous Sodium Iodate Administration Induces Macula-Specific RPE Damage and Rod-Dominant Apoptosis in the Cynomolgus Monkey.","authors":"Shoji Notomi, Guannan Wu, Takaharu Nagaoka, Nao Yotsumoto, Tomoaki Araki, Mitsuru Arima, Toshio Hisatomi, Koh-Hei Sonoda, Kazutoshi Sawada","doi":"10.1167/iovs.66.9.18","DOIUrl":"10.1167/iovs.66.9.18","url":null,"abstract":"<p><strong>Purpose: </strong>Although sodium-iodate (SI)-induced retinal degeneration has been extensively studied in rodent models, its macular pathology and cone/rod vulnerability difference remains elusive. This study aims to characterize SI-induced macular pathology in cynomolgus monkeys.</p><p><strong>Methods: </strong>Intravenous injections of SI were performed on four male cynomolgus monkeys including three young adults (Animal No. 1-3; five to six years old) and one juvenile (Animal No. 4; two years old) from a breeding colony. To optimize dosing, Animal No. 1 received 25 and 37.5 mg/kg SI; Animal No. 2 received a single SI dose (30 mg/kg) to confirm reproducibility. Animal No. 3 was used to examine subclinical effects at a lower dose (25 mg/kg). Animal No. 4 received increasing doses (30, 35, and 40 mg/kg). Retinal changes were evaluated using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). Histological analysis and transmission electron microscopy (TEM) were also performed.</p><p><strong>Results: </strong>In Animal No. 1, prominent fluorescein leakage by FA and RPE elevation on OCT was observed in the macula after 37.5 mg/kg SI. Histology and TEM revealed that elevated RPE lesion was accompanied by significant RPE migration. Animal No. 2 exhibited similar retinal degeneration. Animal No. 3 exhibited no RPE barrier disruption but showed outer segment damage and RPE melanolipofuscin accumulation. Animal No. 4 showed minimal macular degeneration despite escalating doses. In the peripheral retina, rod apoptosis was evident, whereas macular cone cell death was limited even at high doses.</p><p><strong>Conclusion: </strong>Systemic SI administration can induce macular degeneration with RPE barrier disruption in young-adult monkeys, supporting a macula- and cell-type-specific vulnerability.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12248985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583880","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":"Hyperreflective Foci in the Ectopic Inner Foveal Layer of Advanced Idiopathic Epiretinal Membranes.","authors":"Nicola Valsecchi, Maurizio Mete, Giulio Rapezzi, Matteo Elifani, Giulia Folgaria, Alessandro Finzi, Antonio Moramarco, Luigi Fontana","doi":"10.1167/iovs.66.9.14","DOIUrl":"10.1167/iovs.66.9.14","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the presence of hyperreflective foci (HF) in the ectopic inner foveal layer (EIFL) of eyes with advanced idiopathic epiretinal membranes (iERMs) before and after pars plana vitrectomy (PPV) with ERM peeling.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on clinical records and spectral-domain optical coherence tomography (SD-OCT) scans from consecutive patients who underwent PPV with ERM peeling. Stage 3 and stage 4 iERMs were included. HF were defined as dot-like lesions (<30 µm) with reflectivity similar to that of the retinal nerve fiber layer, lacking backshadowing, located in the EIFL thickness within 1500 µm of the fovea. Patients were followed up to twelve months after surgery.</p><p><strong>Results: </strong>A total of 47 eyes were included: 10 stage 4 iERM and 37 stage 3 iERM. HF in EIFLs were observed in 74.5% of cases, with higher prevalence in stage 4 than stage 3 (100% vs. 67.6%; P = 0.035). At baseline, an increase in HF count was associated with greater EIFL thickness (r = 0.497, P < 0.001). At 7.8 ± 1.8 months post-surgery, HF were found in 59.6% of eyes. Eyes with persistent HF had greater postoperative EIFL thickness than those without (143 ± 60.4 vs. 103.7 ± 57.3; P = 0.036). In multivariate linear regression, the presence of HF at baseline (β = 0.373, P = 0.048) was significantly associated with worse postoperative visual acuity.</p><p><strong>Conclusions: </strong>HF in the EIFL were more prevalent in advanced iERM and correlated with increased EIFL thickness. Their presence at baseline was associated with worse postoperative visual acuity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575497","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":"Quantitative Choroidal Analysis of Molecularly Characterized Retinitis Pigmentosa.","authors":"Kirk A J Stephenson, Tiffany Tse, Jiwon Hwang, Andrii Kavetskyi, Shanil R Dhanji, Olubayo U Kolawole, Cheryl Y Gregory-Evans, Kaivon Pakzad-Vaezi, Zaid N Mammo, Kevin Gregory-Evans, Myeong Jin Ju","doi":"10.1167/iovs.66.9.11","DOIUrl":"10.1167/iovs.66.9.11","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a genetically diverse progressive retinal degeneration with many biomarkers. Detailed retinal phenotypes are described using multimodal imaging, however choroidal characteristics remain ill-defined. We report the first quantitative choroidal evaluation in molecularly characterized RP and assess relationships with retinal structure and function.</p><p><strong>Methods: </strong>Patients with genetically confirmed RP who had optical coherence tomography images and best-corrected visual acuity (BCVA) were assessed. Optical coherence tomography images were manually segmented (ITKSnap) calculating choroidal thickness (CT), choroidal area (CA), and choroidal volume (CV). The choroidal vascularity index (CVI) was calculated with ImageJ. Comparisons were made between X-linked (RPGR), autosomal-recessive (USH2A), and autosomal-dominant (RHO, PRPF31) genotypes, including comparisons for choroidal/retinal parameters, BCVA, and spherical equivalent (SE).</p><p><strong>Results: </strong>Sixty-five patients (mean age, 47.3 ± 19.5 years; 52.3% female) met the inclusion criteria. CT was thinner in RP patients than controls (P = 0.003). A thinner choroid was associated with older age (r = -0.512; P < 0.001) and worse BCVA (r = 0.298, P = 0.002) but not SE (P = 0.194). Although variable, no statistically significant differences were found for choroidal measures between groups. Leptochoroid (≤100 µm) was associated with advanced age (P < 0.001) and worse BCVA (P = 0.032), but not greater myopia (P = 0. 533). Greater CVI was only associated with better BCVA (P < 0.001) and no other parameters.</p><p><strong>Conclusions: </strong>We report the first quantitative choroidal assessment in a cohort with genetically characterized RP. CT changes in RP are not explained solely by age-related choroidal thinning, nor by SE but seem to be dynamic and reactive to degree and rate of retinal degeneration.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"11"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144553590","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":"Predictors of Final Visual Outcome in Patients With Leber Hereditary Optic Neuropathy Treated With Lenadogene Nolparvovec Gene Therapy.","authors":"Robert C Sergott, Valerio Carelli, Nancy J Newman, Valérie Biousse, Patrick Yu-Wai-Man, Catherine Vignal-Clermont, Constant Josse, Magali Taiel, José-Alain Sahel, Piero Barboni","doi":"10.1167/iovs.66.9.42","DOIUrl":"10.1167/iovs.66.9.42","url":null,"abstract":"<p><strong>Purpose: </strong>This exploratory analysis aimed to identify predictive factors of final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A mutation who received lenadogene nolparvovec gene therapy.</p><p><strong>Methods: </strong>The following covariates were individually evaluated as possible factors associated with improved final BCVA: age, gender, timing of treatment, baseline BCVA value, and baseline optical coherence tomography (OCT) parameters. Univariate analyses were performed from three phase 3 studies (RESCUE, REVERSE, and REFLECT), using BCVA at 1.5 years post-treatment as the dependent variable.</p><p><strong>Results: </strong>In 113 eyes treated at least 6 months after disease onset, the covariates statistically significantly associated with an improvement in final BCVA after having reached a nadir were thicker OCT measurements at baseline-specifically, outer segments of the macular ganglion cell layer (GCL) (superior, temporal, inferior, and nasal) and retinal nerve fiber layer (RNFL) quadrants (superior, inferior, and nasal) (P < 0.05). The largest effects were observed in the thickness of the superior outer GCL segments at baseline (-0.28 logMAR; 95% confidence interval [CI], -0.41 to -0.16) and temporal outer GCL segments at baseline (-0.26 logMAR; 95% CI, -0.38 to -0.13; both P <0.001). A better baseline BCVA in the dynamic phase of the disease was associated with a better final BCVA (-0.09 logMAR; 95% CI, -0.11 to -0.08; P < 0.0001).</p><p><strong>Conclusions: </strong>Better baseline BCVA values and baseline thicker GCL and RNFL at OCT measurements are key predictive factors of the improved BCVA 1.5 years after treatment in patients with MT-ND4 LHON who received lenadogene nolparvovec at least 6 months after disease onset.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"42"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637068","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":"Interocular Differences in Retinal Curvature in Anisometropic Patients and Their Association With Myopic Degree Differences.","authors":"Gongpeng Sun, Muga Emu, Rong Lin, Jing Gong, Ling Zhao, Chunyan Lei, Bi Yang, Ke Ma, Meixia Zhang","doi":"10.1167/iovs.66.9.31","DOIUrl":"10.1167/iovs.66.9.31","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate regional differences in Gaussian retinal curvature (RC) between fellow eyes of anisometropic patients and their associations with interocular disparities in myopic parameters.</p><p><strong>Methods: </strong>In this cross-sectional study, ultra-widefield swept-source optical coherence tomography (24 mm × 20 mm field) was performed in 121 anisometropic patients. Three-dimensional retinal morphology reconstruction based on Bruch's membrane was used to derive Gaussian RC. The retina was segmented into macular, peripheral, and six concentric annular regions (I-VI). Paired t-tests or Wilcoxon signed-rank tests were applied to evaluate interocular RC differences, with Spearman correlation analysis examining associations between RC variations and myopic parameter disparities.</p><p><strong>Results: </strong>Mean interocular differences were 1.95 ± 0.95 D for spherical equivalent (SE) and 0.79 ± 0.46 mm for axial length (AL). The more myopic eye exhibited significantly steeper macular RC (P < 0.001) and flatter peripheral RC (P < 0.001) compared to the fellow eye. Macular/peripheral RC disparities demonstrated significant correlations with SE/AL differences (both P < 0.05). Region-specific analysis revealed positive correlations between AL and RC I-III differentials, whereas inverse correlations were observed for RC V-VI (all P < 0.01).</p><p><strong>Conclusions: </strong>Anisometropic patients demonstrate biomechanical divergence characterized by macular steepening and peripheral flattening in the more myopic eye during axial elongation, suggesting region-dependent retinal adaptation mechanisms.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"31"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608434","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":"Retinal Angiogenesis in Methamphetamine Self-Administration Rats.","authors":"Minsup Lee, Bo J Wood, Hyeon Hak Jeong, Hyung W Nam, Courtney M Keller, Bonggi Lee, Jae-Il Kim, Kevin S Murnane, Nicholas E Goeders, Norman R Harris","doi":"10.1167/iovs.66.9.8","DOIUrl":"10.1167/iovs.66.9.8","url":null,"abstract":"<p><strong>Purpose: </strong>Given the evidence of a link between methamphetamine (METH) exposure and retinal vascular abnormalities, this study aims to investigate the molecular and cellular mechanisms underlying METH-induced retinal angiogenesis using a unique self-administration rat model and primary rat retinal microvascular endothelial cells (RRMECs).</p><p><strong>Method: </strong>To model the impact of compulsive use of METH, rats underwent an 8-week METH long-access self-administration protocol, with retinal tissues analyzed using whole retinal flatmount imaging and vascular network quantification. Proteomic analysis via liquid chromatography/tandem mass spectrometry identified differentially expressed proteins, while RRMECs were treated with METH to assess molecular changes through immunoblotting and quantitative RT-PCR.</p><p><strong>Results: </strong>Consistent with compulsive use of METH in humans and our previous experience with this model, rats self-administered high levels of METH. METH self-administration elevated dopamine levels in the vitreous humor and increased vascular density in both superficial and deep capillary layers across central, mid-peripheral, and peripheral retina regions. Proteomic analysis revealed 148 differentially expressed retinal proteins, with gene ontology enrichment highlighting pathways related to abiotic stimuli, hypoxia, and ischemia. Increased hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor a (VEGFa) expression confirmed a hypoxia-driven angiogenesis process, further supported by in vitro experiments showing enhanced endothelial cell proliferation and HIF-1α/VEGFa expression. Additionally, TAAR-1 upregulation in both the retina and endothelial cells was observed, with TAAR-1 antagonism reducing METH-induced endothelial cell proliferation and modulating HIF-1α/VEGFa signaling.</p><p><strong>Conclusions: </strong>METH self-administration leads to significant retinal vascular changes and angiogenesis, driven by upregulation of hypoxia-related pathways. TAAR-1 plays a critical role in endothelial cell proliferation through the HIF-1α/VEGFa pathway, potentially contributing to pathological retinal conditions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540235","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":"Risk Factors for Visual Field Progression in Primary Angle Closure Disease Over 10 Years: The CUPAL Study.","authors":"Ruyue Shen, Poemen P Chan, Anni Ling, Noel C Y Chan, Mandy Oi-Man Wong, Isabel Lai, Carol Y Cheung, Clement C Tham","doi":"10.1167/iovs.66.9.59","DOIUrl":"10.1167/iovs.66.9.59","url":null,"abstract":"<p><strong>Purpose: </strong>To identify associated long-term risk factors of visual field (VF) progression among eyes of primary angle-closure disease (PACD), including primary angle-closure suspect (PACS), primary angle-closure (PAC), and primary angle-closure glaucoma (PACG).</p><p><strong>Methods: </strong>PACD eyes with at least a 10-year follow-up duration were included. VF was tested every 6 months using the 24-2 pattern standard on the Humphrey Field Analyzer. The initial intraocular pressure (IOP) fluctuation and initial visual field index (VFI) slope were calculated based on the first-year follow-up data. Univariable and multivariable Cox proportional hazards regression models were calculated to determine potential risk factors associated with VF progression, as assessed by guided progression analysis.</p><p><strong>Results: </strong>Forty out of 129 eyes with PACD (31.0%) developed VF progression, including two out of 11 PACS eyes (18.2%), nine out of 52 PAC eyes (17.3%), and 29 out of 66 PACG eyes (43.9%). In multivariable Cox models, among PACG eyes, higher IOP fluctuation (hazard ratio [HR] = 1.591; 95% confidence interval [CI], 1.128-2.245) and steeper initial VFI slope (HR = 3.325; 95% CI, 2.046-5.404) were associated with VF progression. Among PACS/PAC eyes, a steeper initial VFI slope (HR = 4.848; 95% CI, 1.627-14.448) was associated with VF progression (P ≤ 0.008).</p><p><strong>Conclusions: </strong>Our findings underscore the importance of monitoring IOP fluctuation in PACG eyes and initial VFI slope in PACD eyes, supporting the implementation of tailored management strategies based on disease severity and refractive status.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"59"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690304","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}