Investigative ophthalmology & visual science最新文献

{"title":"Impact of Second-Generation PDE 5 Inhibitor, Avanafil, on Retinal Function: Studies From Ex Vivo ERG.","authors":"Sama Saeid, Frans Vinberg, Ari Koskelainen","doi":"10.1167/iovs.66.6.14","DOIUrl":"10.1167/iovs.66.6.14","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates whether avanafil, a second-generation phosphodiesterase 5 (PDE5) inhibitor, exhibits reduced off-target effects on retinal function compared to first-generation inhibitors, by quantifying its impact on photoreceptor and bipolar cell signaling using transretinal electroretinography (tERG).</p><p><strong>Methods: </strong>We conducted ex vivo tERG using wild-type C57BL/6J and Gnat-/- mice. The dark-adapted isolated retinas were stimulated with 530-nm full-field flashes of light while perfused with controlled avanafil concentrations at 0.1, 0.3, 1, 3, and 10 µM. The inhibition constant of avanafil for light-activated phosphodiesterase 6 (PDE6) was determined from flash responses for rods and cones. The effects of avanafil on bipolar cell signaling were also assessed.</p><p><strong>Results: </strong>Avanafil exhibited dose-dependent inhibition of rod and cone phototransduction, characterized by slower response kinetics and reduced amplitude of dim flash responses. The inhibition constants for light-activated PDE6 were determined to be 1.74 µM for rods and 6.3 µM for cones. This study demonstrated that avanafil does not inhibit spontaneous PDE6 activity, and it has a lower inhibitory effect on light-activated PDE6 compared to other PDE5 inhibitors like sildenafil and zaprinast. Additionally, we conclude that avanafil primarily impacts photoreceptor cells, with no significant direct effect on rod bipolar cell signaling.</p><p><strong>Conclusions: </strong>This study provides quantitative insights into avanafil's impact on retinal function, supporting the hypothesis that it has reduced off-target effects on PDE6 and retinal signaling.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12147044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215826","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: Comparison of Physiological Brain Responses Evoked by Visual and Electrical Stimulation.","authors":"","doi":"10.1167/iovs.66.6.46","DOIUrl":"10.1167/iovs.66.6.46","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"46"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144284392","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":"Hyperopic Eyes Are Structurally More Dynamic Than Myopic Eyes During Accommodation: An In Vivo Investigation.","authors":"Tuyishime Didier Fidele Uwacu, Saugat Bhattacharyya, Kathryn J Saunders, Julie-Anne Little","doi":"10.1167/iovs.66.6.51","DOIUrl":"10.1167/iovs.66.6.51","url":null,"abstract":"<p><strong>Purpose: </strong>The impact of different refractive errors on accommodative structural changes remains unclear. Novel swept-source imaging technology in anterior segment optical coherence tomography (AS-OCT) has enabled in vivo investigation of the accommodating eye. This study investigated ocular structural change and corresponding functional responses during accommodation in individuals with emmetropia, myopia, and hyperopia.</p><p><strong>Methods: </strong>Adults (n = 46; mean age, 22.15 ± 3.00 years) with normal accommodation and a wide range of refractive errors (spherical equivalent refraction [SER]: -7.50 D to +7.88 D) were recruited. CASIA2 AS-OCT measured anterior segment changes during accommodation stimulated by the use of inbuilt accommodative targets and bespoke external stimuli at five different accommodative demands (0 D, 2 D, 3 D, 4 D, and 6 D) and under cycloplegia. Simultaneously, changes in refractive state were measured using the PowerRefractor3 photorefraction system.</p><p><strong>Results: </strong>Lens thickness (LT), anterior chamber depth (ACD), lens diameter (LD), anterior segment length (ASL), anterior lens radius of curvature (ALRC), and posterior lens radius of curvature (PLRC) changed significantly during accommodation (all P < 0.001). Accommodative changes in LT, ACD, and ASL were significantly associated with the level of SER (all P < 0.05), as more hyperopic eyes showed significantly greater per-diopter change than myopic eyes in LT (P = 0.014) and ACD (P = 0.039) for comparatively similar accommodative response (P > 0.9). The analysis of lens position showed that cycloplegia induced posterior displacement of the lens. The CASIA2 internal accommodative target and the external proximal target induced similar structural and functional accommodative responses.</p><p><strong>Conclusions: </strong>There are significant differences between structural changes seen in accommodating eyes with different types and magnitudes of refractive error, with hyperopic eyes showing greater changes in LT and ACD than myopic eyes during accommodation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"51"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302081","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":"Human Platelet Lysate Treatment for Exposure Keratopathy: An In Vivo Confocal Microscopy and Anterior Segment OCT Study.","authors":"Chia-Ying Tsai, Wei-Lun Huang, Shang-Chih Yang, Bo-Da Huang, Vladlen Klochkov, Shu-Lang Liao, Albert Y Wu, Wei-Li Chen","doi":"10.1167/iovs.66.6.73","DOIUrl":"10.1167/iovs.66.6.73","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effects of topical human platelet lysate (HPL) on exposure keratopathy (EK) in a rabbit model, with a focus on its anti-inflammatory and anti-dehydration properties on the cornea.</p><p><strong>Methods: </strong>Short-term exposure keratopathy was induced in New Zealand albino rabbits by keeping the eyelids open for four hours, followed by eyelid closure for another four hours, during which the treatment was applied. HPL, fetal bovine serum (FBS), or preservative-free artificial tears (PFAT) were administered every 15 minutes, and corticosteroid was applied every one hour during the treatment period. Corneal thickness changes and epithelial defects were assessed using anterior segment optical coherence tomography (AS-OCT) and fluorescein staining. In vivo confocal microscopy (IVCM) was used to evaluate inflammatory cell infiltration, whereas immunohistochemistry (IHC) was performed to confirm the presence of CD8+ T cells, neutrophils, and macrophages and the cell proliferation marker Ki67.</p><p><strong>Results: </strong>After completing the treatment, no significant difference in fluorescein staining was observed among the four groups. However, AS-OCT revealed more effective recovery of corneal thinning in the HPL- and FBS-treated groups, including improvements in epithelial, stromal, and total corneal thickness. IVCM revealed significantly reduced infiltration of inflammatory cells in the HPL-, FBS-, and corticosteroid-treated groups compared to the PFAT-treated group across the central cornea, peripheral cornea, and conjunctiva. IHC for CD8+ T cells, neutrophils, and macrophages showed similar findings. HPL-treated groups showed more Ki-67-positive cells compared to the PFAT- and corticosteroid-treated groups.</p><p><strong>Conclusions: </strong>HPL treatment effectively reduced inflammation, promoted the recovery of corneal thickness, and induced cellular proliferation after dehydration, demonstrating its potential as a treatment for EK.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"73"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475178","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":"Cornea Nerves Can Identify Different Types of Parkinson's Disease.","authors":"Dongyu Li, Xinyu Zhang, Fan Yang, Xin Jin, Shumin Li, Haonan Yuan, Lifen Yao, Hong Zhang","doi":"10.1167/iovs.66.6.21","DOIUrl":"10.1167/iovs.66.6.21","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate whether the cornea nerve can distinguish between different subtypes of Parkinson's disease.</p><p><strong>Methods: </strong>A total of 63 patients diagnosed with Parkinson's disease-comprising tremor-dominant (TD), postural instability and gait disturbance (PIGD), and mixed subtypes-were included alongside 31 age- and gender-matched control participants. All participants underwent In vivo confocal microscopy (IVCM) examinations along with comprehensive assessments of clinical neurological symptoms using the Movement Disorders Society Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stages, and Montreal Cognitive Assessment scores. The detection range of IVCM includes the indicators of central and inferior whorl-like cornea nerve.</p><p><strong>Results: </strong>This study involved 63 patients, 23 were classified as having the TD type, 30 as having the PIGD type, and 10 as mixed type. Among them, most of central and whorl-like corneal nerve indicators were significantly lower in the PIGD group compared to the TD group. Receiver operating characteristic analysis demonstrated that combined central and inferior whorl-like corneal nerve indicators exhibited high discriminatory power between TD and PIGD types, with an area under the curve of 0.969.</p><p><strong>Conclusions: </strong>As a non-invasive examination method, IVCM holds significant value for differentiating Parkinson's disease subtypes and identifying patients with varying motor manifestations. Among these findings, individuals with PIGD displayed more pronounced corneal nerve damage; furthermore, patients exhibiting lower inferior whorl length, corneal nerve fiber width, and fractal dimension of corneal nerves values were found to be at greater risk of being classified within the PIGD subtype.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"21"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234105","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":"Generation of a Mouse Model of Fuchs Endothelial Corneal Dystrophy by Knock-in of CTG Trinucleotide Repeat Expansion in the TCF4 Gene.","authors":"Yuki Oyama, Suguru Ito, Taichi Yuasa, Mizuki Ueda, Satoshi Chiba, Tatsuya Nakagawa, Ayaka Izumi, Masahito Ikawa, Noriko Koizumi, Naoki Okumura","doi":"10.1167/iovs.66.6.18","DOIUrl":"10.1167/iovs.66.6.18","url":null,"abstract":"<p><strong>Purpose: </strong>Fuchs endothelial corneal dystrophy (FECD) is frequently associated with trinucleotide repeat (TNR) expansion in the TCF4 gene intron. The aim of this study was to establish a novel FECD mouse model with TNR expansion.</p><p><strong>Methods: </strong>We used CRISPR/Cas9-mediated genome editing to generate knock-in mice carrying 100 CTG repeats in the Tcf4 intron. Corneal endothelial phenotypes were evaluated using specular microscopy and transmission electron microscopy. Transcriptome analysis was performed using RNA sequencing of corneal endothelial tissue from Tcf4(CTG)100/(CTG)100 and wild-type mice.</p><p><strong>Results: </strong>Tcf4+/(CTG)100 and Tcf4(CTG)100/(CTG)100 mice developed characteristic FECD features, including progressive guttae formation and decreased corneal endothelial cell density. At 60 weeks, Tcf4+/(CTG)100 mice showed increased guttae percentage (0.314% ± 0.145%) versus wild-type (0.170% ± 0.089%), although not statistically significant. Tcf4(CTG)100/(CTG)100 mice exhibited significantly higher guttae formation (0.563% ± 0.293%) compared to controls. Similarly, endothelial cell density showed non-significant reduction in Tcf4+/(CTG)100 (1629 ± 71 cells/mm2) versus wild-type (1704 ± 68 cells/mm2), whereas Tcf4(CTG)100/(CTG)100 mice demonstrated significant decrease (1600 ± 76 cells/mm2). RNA sequencing identified 3221 differentially expressed genes (579 upregulated, 2,642 downregulated), with enrichment in pathways related to adaptive immune response, chemokine signaling, and cytokine-cytokine receptor interaction.</p><p><strong>Conclusions: </strong>Our study demonstrates that TNR expansion in the Tcf4 intron, on its own, is sufficient to induce FECD phenotypes in vivo. This mouse model provides a valuable tool for investigating FECD pathogenesis and developing targeted therapeutics.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215825","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: Treatment of Pathological Lymphangiogenesis via Circular RNA-Mediated Cholesterol Metabolism Remodeling.","authors":"","doi":"10.1167/iovs.66.6.26","DOIUrl":"10.1167/iovs.66.6.26","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"26"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155654/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234106","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":"SLC6A6-Mediated Taurine Uptake Sustains Corneal Epithelial Stem/Progenitor Cell Function to Counteract Age-Related Dysfunction.","authors":"Yizhou Li, Feijia Xie, Lingling Yang, Xiaolei Wang, Yangyang Zhang, Hongqi Ge, Min Wang, Rui Cao, Qingjun Zhou, Ya Li","doi":"10.1167/iovs.66.6.25","DOIUrl":"10.1167/iovs.66.6.25","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate the role of SLC6A6-mediated taurine transport in maintaining corneal limbal stem/progenitor cell (LSPC) function and its implications for age-associated corneal wound healing.</p><p><strong>Methods: </strong>Corneal amino acid profiles from C57BL/6J mice were analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). SLC6A6 expression patterns were mapped using single-cell RNA sequencing, quantitative PCR, and immunofluorescence. Pharmacological inhibition of SLC6A6 with guanidinoethyl sulfonate (GES) was applied in corneal wound healing models and murine corneal epithelial stem/progenitor (TKE2) cells. Transcriptomic profiling, RNA/protein analyses, and functional assays were performed in GES-treated TKE2 cells. Aged mice with corneal epithelium scraping received topical taurine supplementation (25 mg/mL, 5 times/day), and the corneas were collected for immunofluorescence staining. Moreover, TKE2 cells were treated with GES along with the Notch1 agonist valproic acid (VPA), or they were treated with taurine along with the Notch1 inhibitor GSI-IX (DAPT).</p><p><strong>Results: </strong>The cornea exhibited high taurine concentrations, with its transporter SLC6A6 predominantly localized in LSPCs (limbal stem cells, transient amplifying cells, and basal cells) and displaying age-dependent expression patterns. SLC6A6 inhibition delayed corneal wound healing, triggered senescence pathway activation and pluripotency suppression, and downregulated stemness markers (BCAM, p63, KRT14, Wnt4) and proliferative markers (Ki67), which recapitulated key features of corneal aging. This functional decline was reversed through topical taurine supplementation. Moreover, VPA effectively reversed the inhibitory effect of GES, whereas DAPT attenuated the effect of taurine, indicating involvement of the Notch1 signaling pathway in taurine-induced LSPC maintenance.</p><p><strong>Conclusions: </strong>SLC6A6-driven taurine uptake critically regulates LSPC homeostasis, presenting a therapeutic strategy for age-related corneal disorders.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"25"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12155693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234110","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":"Associations Between Myopia and Brain Volumes: An Observational and Genetic Analysis.","authors":"Selena Wei Zhang, Jingze Guo, Yanxian Chen, Jiahao Liu, Yu Huang, Xianwen Shang, Mingguang He","doi":"10.1167/iovs.66.6.57","DOIUrl":"10.1167/iovs.66.6.57","url":null,"abstract":"<p><strong>Purpose: </strong>To examine phenotypic and genetic associations between myopia and various brain volumes using the UK Biobank database.</p><p><strong>Methods: </strong>After 1:1 propensity score matching (PSM) between participants with myopia and healthy controls, the relationship between myopia and brain volumes was examined using general linear regression, with adjustments for covariates including age, sex, ethnicity, Townsend Deprivation Index, lifestyle factors, and disease status. Bonferroni correction was applied for multiple comparisons. Bidirectional Mendelian randomization (MR) and genetic risk score (GRS) were used to assess genetic associations.</p><p><strong>Results: </strong>After Bonferroni correction, general linear regression revealed that myopia was significantly associated with reduced total brain volume (β, -0.07 mL; 95% confidence interval [CI], -0.11 to -0.03) and white matter volume (β, -0.08 mL; 95% CI, -0.13 to -0.03) in the fully adjusted model. Education significantly modified the myopia-gray matter association, with a stronger negative correlation in individuals without a college education (β, -0.09 mL; 95% CI, -0.15 to -0.04). MR analysis indicated no obvious causal effect of myopia on brain volumes, and GRS analysis revealed only a slight decreasing trend in total brain volume with increasing genetic risk for myopia (P value for trend < 0.05).</p><p><strong>Conclusions: </strong>Although myopia shows phenotypic associations with brain volumes, including total brain and white matter, and particularly with gray matter in individuals with lower education, genetic analysis (MR and GRS) did not support a causal or genetic link with brain volumes. These findings suggest that residual confounding factors beyond education level may underlie the observed associations between myopia and brain volumes, underscoring the need for further research to elucidate these relationships.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"57"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12180605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144325720","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":"Evaluation of Anti-VEGFR2 Specific Photoimmunotherapy for Targeted Regression of Neovascularization in an AMD Model.","authors":"Hideto Osada, Takashi Nishimura, Makoto Mitsunaga, Masayuki Saruta, Kazuo Tsubota, Kazuno Negishi, Toshihide Kurihara, Norimitsu Ban","doi":"10.1167/iovs.66.6.70","DOIUrl":"10.1167/iovs.66.6.70","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the efficacy of photoimmunotherapy (PIT) targeting VEGFR2 for the treatment of neovascular AMD and to investigate its potential as a novel therapeutic strategy.</p><p><strong>Methods: </strong>DC101-IR700, a conjugate of the anti-mouse VEGFR2 monoclonal antibody DC101 and the photosensitizer IR700, was investigated both in vitro and in vivo. VEGFR2 expression in endothelial cells was confirmed via qPCR and immunocytochemistry. Laser-induced choroidal neovascularization (CNV) was established in C57BL/6J mice. Localization of DC101-IR700 within CNV lesions was assessed by immunofluorescence. After PIT was performed using either a 690 nm near-infrared manual laser or a slit lamp laser, CNV volumes were quantified through confocal microscopy. Cell viability post PIT was measured using MTT assay and cell death in CNV lesions was evaluated using TUNEL staining.</p><p><strong>Results: </strong>DC101-IR700 localized specifically to VEGFR2-positive cells in CNV lesions, and PIT induced significant VEGFR2-dependent cytotoxicity in vitro. In vivo, both PIT and directional PIT using slit lamp laser significantly reduced CNV volumes compared with controls. TUNEL staining confirmed VEGFR2-specific cell death in treated CNV lesions. Directional PIT achieved similar efficacy to PIT, demonstrating its potential as a clinically viable alternative.</p><p><strong>Conclusions: </strong>PIT targeting VEGFR2 selectively induced cell death in pathological neovascular tissues, significantly reducing CNV volume in an AMD model. These findings suggest that VEGFR2-specific PIT represents a promising and targeted approach for treating neovascular AMD, offering advantages over conventional anti-VEGF therapies by potentially decreasing treatment frequency and improving efficacy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"70"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475166","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}