Investigative ophthalmology & visual science最新文献

{"title":"Glucagon-Like Peptide 1 Receptor Agonist Stimulation Inhibits Laser-Induced Choroidal Neovascularization by Suppressing Intraocular Inflammation.","authors":"Akira Machida, Keiji Suzuki, Takafumi Nakayama, Sugao Miyagi, Yuki Maekawa, Ryuya Murakami, Masafumi Uematsu, Takashi Kitaoka, Akio Oishi","doi":"10.1167/iovs.66.5.15","DOIUrl":"https://doi.org/10.1167/iovs.66.5.15","url":null,"abstract":"<p><strong>Purpose: </strong>The glucagon-like peptide-1 receptor (GLP-1R), a diabetes therapy target, is expressed in multiple organs and is associated with neuroprotective, anti-inflammatory, and antitumor effects, particularly in cardiac and cerebral tissues. Although GLP-1's role in diabetic and ischemic retinopathies is well-studied, its influence on choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD) remains unclear. This study explored the effects of GLP-1 on CNV using a laser-induced mouse model.</p><p><strong>Methods: </strong>The anti-angiogenic effects of GLP-1 were tested using ex vivo sprouting assays in 3-week-old C57BL/6J mice. In 6-week-old mice, GLP-1R localization in laser-induced CNV lesions was analyzed via immunohistochemistry. Liraglutide, a GLP-1R agonist, was administered subcutaneously for 7 days or by single intravitreal injection post-laser. Eyeballs collected on days 1 to 7 post-laser were analyzed using RT-qPCR for GLP-1R expression and inflammatory cytokines.</p><p><strong>Results: </strong>GLP-1R-positive cells were detected in CNV lesions and were expressed in Iba-1-positive activated microglia or macrophages. They also expressed in abnormal retinal pigment epithelial cells and surrounding normal endothelial cells. NOD-like receptor protein 3 (NLRP3) inflammasome signaling was observed near CNV. Liraglutide inhibited angiogenesis in ex vivo assays and significantly reduced CNV formation with both subcutaneous and intravitreal administration. Additionally, Liraglutide inhibited expression of NLRP3, IL-1β, IL-6, and TNF expression compared with healthy controls. Intravitreal GLP-1R antagonist reduced subcutaneous effects.</p><p><strong>Conclusions: </strong>Liraglutide suppresses CNV formation, likely via NLRP3 inflammasome inhibition. Intraocular GLP-1R appears to mediate anti-CNV effects, supporting GLP-1R agonists as potential adjunctive therapy for exudative AMD and warranting further investigation into its safety and clinical feasibility.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144008986","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":"Systematic Ocular Phenotyping of Knockout Mouse Lines Identifies Genes Associated With Age-Related Corneal Dystrophies.","authors":"Andrew Briere, Peter Vo, Benjamin Yang, David Adams, Takanori Amano, Oana Amarie, Zorana Berberovic, Lynette Bower, Steve D M Brown, Samantha Burrill, Soo Young Cho, Sharon Clementson-Mobbs, Abigail D'souza, Mohammad Eskandarian, Ann M Flenniken, Helmut Fuchs, Valerie Gailus-Durner, Yann Hérault, Martin Hrabe de Angelis, Shundan Jin, Russell Joynson, Yeon Kyung Kang, Haerim Kim, Hiroshi Masuya, Hamid Meziane, Ki-Hoan Nam, Hyuna Noh, Lauryl M J Nutter, Marcela Palkova, Jan Prochazka, Miles Joseph Raishbrook, Fabrice Riet, Jason Salazar, Radislav Sedlacek, Mohammed Selloum, Kyoung Yul Seo, Je Kyung Seong, Hae-Sol Shin, Toshihiko Shiroishi, Michelle Stewart, Karen Svenson, Masaru Tamura, Heather Tolentino, Sara Wells, Wolfgang Wurst, Atsushi Yoshiki, Louise Lanoue, K C Kent Lloyd, Brian C Leonard, Michel J Roux, Colin McKerlie, Ala Moshiri","doi":"10.1167/iovs.66.5.7","DOIUrl":"https://doi.org/10.1167/iovs.66.5.7","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates genes contributing to late-adult corneal dystrophies (LACDs) in aged mice, with potential implications for late-onset corneal dystrophies (CDs) in humans.</p><p><strong>Methods: </strong>The International Mouse Phenotyping Consortium (IMPC) database, containing data from 8901 knockout mouse lines, was filtered to include late-adult mice (49+ weeks) with significant (P < 0.0001) CD phenotypes. Candidate genes were mapped to human orthologs using the Mouse Genome Informatics group, with expression analyzed via PLAE and a literature review for prior CD associations. Comparative analyses of LACD genes from IMPC and established human CD genes from IC3D included protein interactions (STRING), biological processes (PANTHER), and molecular pathways (KEGG).</p><p><strong>Results: </strong>Analysis identified 14 genes linked to late-adult abnormal corneal phenotypes. Of these, 2 genes were previously associated with CDs in humans, while 12 were novel. Seven of the 14 genes (50%) were expressed in the human cornea based on single-cell transcriptomics. Protein-protein interactions via STRING showed several significant interactions with known human CD genes. PANTHER analysis identified six biological processes shared with established human CD genes. Two genes (Rgs2 and Galnt9) were involved in pathways related to human corneal diseases, including cGMP-PKG signaling, mucin-type O-glycan biosynthesis, and oxytocin signaling. Other candidates were implicated in pathways such as pluripotency of stem cells, MAPK signaling, WNT signaling, actin cytoskeleton regulation, and cellular senescence.</p><p><strong>Conclusions: </strong>This study identified 14 genes linked to LACD in knockout mice, 12 of which are novel in corneal biology. These genes may serve as potential therapeutic targets for treating corneal diseases in aging human populations.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003284","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":"Canonical and Truncated Transglutaminase-2 Drive TGF-β1 Autocrine Loop to Induce Fibrosis in Graves' Orbitopathy.","authors":"Xiaoli Bao, Zhihui Xu, Xi Wang, Te Zhang, Xiaotong Sha, Anqi Sun, Huijing Ye, Huasheng Yang","doi":"10.1167/iovs.66.5.22","DOIUrl":"https://doi.org/10.1167/iovs.66.5.22","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the role of transglutaminase 2 (TGM2) in fibroblasts of Graves' orbitopathy (GO) and explore its potential mechanisms in orbital fibrosis.</p><p><strong>Methods: </strong>A key gene selection model for GO was established through bioinformatics and machine learning. Orbital fibroblasts (OFs) were cultured from orbital connective tissue samples. Subsequently, three-dimensional spheroid models were developed. Lentiviral transduction was used to establish TGM2 overexpression and knockdown models. Fibrosis levels were assessed using Western blot, PCR, and collagen contraction assays. TGM2 activity was evaluated by FITC-cadaverine staining and the colorimetric assay. The canonical and truncated TGM2 isoforms were selectively introduced to restore expression. TGF-β1 levels in cell culture supernatants were measured by ELISA.</p><p><strong>Results: </strong>The results of bioinformatics and machine learning indicate that TGM2 is a key characteristic gene in GO. Knockdown of TGM2 markedly suppresses the expression of fibrosis-related genes and reduces the proliferation, migration, and adhesion capabilities of fibroblasts. TGF-β1 can upregulate TGM2 expression and induces the production of both the canonical and truncated TGM2 forms. Similar results were observed in GO tissues. Restoration of TGM2_V2 expression following knockdown can prevent the inhibitory effects on guanosine triphosphate (GTP). Additionally, TGM2 is involved in the autocrine loop of TGF-β1. TGM2 inhibitors significantly reverse the fibrotic response induced by TGF-β1 in OFs.</p><p><strong>Conclusions: </strong>TGM2 is highly expressed in GO fibroblasts and plays a key role in the TGF-β1 autocrine feedback loop. TGF-β1 induces more truncated TGM2 variants that bypass GTP inhibition, exacerbating fibrosis. Inhibiting TGM2 activity significantly reduces fibrosis markers.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Physiological Brain Responses Evoked by Visual and Electrical Stimulation.","authors":"Katarzyna Kordecka, Ewa Kublik, Andrzej T Foik","doi":"10.1167/iovs.66.5.1","DOIUrl":"https://doi.org/10.1167/iovs.66.5.1","url":null,"abstract":"<p><strong>Purpose: </strong>Noninvasive current stimulation (nCS or electrical stimulation) is a rapidly developing technique to support recovery from eye and brain dysfunctions. One of the most commonly used forms of nCS for treating the visual system is transcranial and transcorneal alternating current stimulation. This technique can exert neuromodulatory effects on the brain through eye stimulation. The mechanism of such stimulation is still poorly understood.</p><p><strong>Materials and methods: </strong>To understand the pattern of activation evoked by nCS, a series of electrical impulses were delivered directly to the rat eye, alternating with the visual stimulus (VS), and subsequent responses were tested in the Superior colliculus and the primary visual cortex. Additionally, we tested two stimulation electrode placements, eyeball-eyeball, and eyeball-neck.</p><p><strong>Results: </strong>The results indicate that nCS and VS evoke different activation patterns in the recorded structures. In particular, the electrically evoked potentials are characterized by shorter latency and a different shape than the corresponding visually evoked potentials. The transcorneal alternating current stimulation (tACS) evoked shorter sinks and sources in all recorded structures than the visual stimulation. This suggests emerging of a different pattern of extracellular current flow in response to different stimulations.</p><p><strong>Conclusions: </strong>We demonstrate that the eye-eye paradigm of electrical stimulation elicited responses more similar to those evoked by VS. Individual transcorneal electrical impulses evoke a consistent pattern of neuronal activation across the visual system. This consistency is particularly promising for the development of neurotherapy aimed at restoring or improving vision, nCS can effectively activate visual circuits despite variations in stimulus delivery and shape.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013381","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":"High Resolution Imaging and Fixation Analysis of Eccentric Preferred Retinal Loci in Macular Diseases.","authors":"Olubayo U Kolawole, Ethan Bensinger, Jessica Wong, Nicholas Rinella, Katharina G Foote, Hao Zhou, Ruikang K Wang, Jacque L Duncan, Austin Roorda","doi":"10.1167/iovs.66.5.18","DOIUrl":"https://doi.org/10.1167/iovs.66.5.18","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to characterize the preferred retinal locus (PRL) structure and fixational eye movements in eyes with macular atrophy.</p><p><strong>Methods: </strong>Four participants (1 each with macular atrophy due to congenital rubella, Best macular dystrophy, cuticular drusen with macular atrophy, and Stargardt disease) were studied using adaptive optics scanning light ophthalmoscopy (AOSLO), optical coherence tomography (OCT), OCT angiography (OCT-A), and microperimetry. Imaging sessions were repeated in three of the four participants. PRL and fixation stability were measured with AOSLO. Fixation stability was compared with healthy participants and participants with RHO- and USH2A-related retinitis pigmentosa (RP).</p><p><strong>Results: </strong>The PRL in participants with eccentric fixation was 0.44 to 1.92 degrees from the anatomic fovea and visual acuity was 20/40 or better. Cones at the PRL were not visible in confocal images, despite normal-appearing and more sensitive cones at greater eccentricities. OCT at the PRL showed intact external limiting membranes but hyporeflective and disrupted inner-segment outer-segment junctions. Fixation stability in participants with eccentric PRLs was no worse than participants with RP, all with foveal PRLs. The eccentric PRL group and the USH2A group with worse visual acuity (20/30 to 20/50) had fixation stabilities that were worse than the healthy controls.</p><p><strong>Conclusions: </strong>Participants adopt eccentric PRLs with hyporeflective cones and reduced sensitivity despite more sensitive and normal-appearing cones at greater eccentricities, suggesting that foveal proximity is prioritized over cone integrity in establishing a PRL. Fixation stability was similar among the four participants with eccentric fixation and those with RP, indicating that small shifts in the PRL from the anatomic fovea in our participants do not make fixation less stable.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12068526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005095","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: Enlarged Blind Spot Linked to Gamma Zone and Peripapillary Hyperreflective Ovoid Mass-Like Structures in Non-Pathological Highly Myopic Eyes.","authors":"","doi":"10.1167/iovs.66.5.16","DOIUrl":"10.1167/iovs.66.5.16","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020919","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":"Endoplasmic Reticulum Stress Drives Neuroinflammation Through Lipocalin 2 Upregulation in Retinal Microglia After Optic Nerve Injury.","authors":"Weifeng Huang, Yaoming Liu, Jinmiao Li, Yang Gao, Junjie Tang, Siuhang Yip, Xinyue Wang, Hongwei Zhang, Yujun Ma, Shicai Su, Jiahe Nie, Rong Lu","doi":"10.1167/iovs.66.5.12","DOIUrl":"https://doi.org/10.1167/iovs.66.5.12","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore how lipocalin 2 (LCN2) connects endoplasmic reticulum (ER) stress and inflammation in optic nerve injury (ONI) and identify potential therapeutic strategies.</p><p><strong>Methods: </strong>An optic nerve crush (ONC) mouse model was used to investigate the role of ER stress and LCN2 in ONI. Immunofluorescence, quantitative PCR, and Western blot analyses were performed to assess ER stress markers, LCN2, inflammation-related genes, and retinal ganglion cell (RGC) survival, with or without treatment of 4PBA (an ER stress inhibitor) and TUN (an ER stress activator) in both the ONC model and BV2 cells. Lcn2 knockdown was achieved using small interfering RNA in BV2 cells and adeno-associated virus (AAV)-mediated gene silencing in vivo to explore underlying signaling pathways.</p><p><strong>Results: </strong>ER stress markers (GRP78, ATF4, CHOP) and LCN2 expression were increased in ONC retinas, accompanied by microglial activation and RGC loss. Inhibition of ER stress using 4PBA effectively decreased LCN2 expression, attenuated microglial activation, and increased RGC survival post-ONC. Intravitreal injection of recombinant LCN2 induced a proinflammatory phenotype in microglia and exacerbated neurotoxicity. AAV-mediated Lcn2 silencing mitigated microglial activation, reduced neuroinflammation, and provided RGC neuroprotection, surpassing 4PBA treatment. In vitro studies further confirmed that Lcn2 knockdown significantly reduced the inflammatory response in BV2 cells by inhibiting NLRP3 inflammasome activation via the TLR4/NF-κB pathway.</p><p><strong>Conclusions: </strong>This study elucidates the critical role of LCN2 in linking ER stress and inflammation in ONI, offering a promising therapeutic target. AAV-mediated Lcn2 silencing outperforms broad ER stress inhibition, providing a novel strategy for treating optic nerve injuries.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000807","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":"Comparative Efficacy of Interleukin-7 and -15 Blockade in Alleviating Experimental Chronic Uveitis and Suppressing Pathogenic Memory CD4+ T Cells.","authors":"Qiurong Zhu, Maryam Shayan, Rachel M Huckfeldt, Yihe Chen","doi":"10.1167/iovs.66.5.9","DOIUrl":"https://doi.org/10.1167/iovs.66.5.9","url":null,"abstract":"<p><strong>Purpose: </strong>We have previously demonstrated the pathogenic function of memory CD4+ T cells, which express IL-7 receptor (IL-7R) and IL-15R, in experimental chronic autoimmune uveitis (CAU). Here, we aimed to compare the therapeutic efficacy of blocking IL-7 or IL-15 in CAU.</p><p><strong>Methods: </strong>C57BL/6J mice were induced for CAU, then intraperitoneally injected with an anti-IL-7 antibody (Ab), an anti-IL-15 Ab, or an IgG control for 2 weeks. Disease was evaluated by weekly fundoscopy, optical coherence tomography (OCT), and full-field electroretinography for four weeks from the initiation of treatment. At week 4, retina and cervical lymph nodes (CLN) were collected for flow cytometry analysis of T-cell response.</p><p><strong>Results: </strong>The anti-IL-7 Ab led to progressively reduced retinal infiltration and structural damage, with rapid recovery of retinal function. The anti-IL-15 Ab resulted in moderately reduced retinal infiltration and structural damage, along with a delayed, partial functional improvement. Compared to the control group, the anti-IL-7 Ab group exhibited significantly reduced disease scores from baseline on fundoscopy and OCT at week 4, and substantially improved dark-adapted (DA) a-wave and light-adapted b-wave responses at week 2; although the anti-IL-15 Ab group showed significantly improved disease from baseline only on OCT and increased DA b-waves at week 4. Both treatments effectively depleted the retinal infiltrating T cells and reduced memory Th17 cells in the CLN.</p><p><strong>Conclusions: </strong>Our proof-of-concept study demonstrates that blocking IL-7 or IL-15 leads to specific depletion of the uveitogenic memory CD4+ T cells and disruption of disease chronicity in uveitis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991478","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-Year Change in Subfoveal Choroidal Thickness and Area With Multifocal Contact Lens Wear in the Bifocal Lenses in Nearsighted Kids (BLINK) Study.","authors":"Maria K Walker, David A Berntsen, Matt L Robich, Rachel L Fenton, Anita Ticak, Justina R Assaad, Hope M Queener, Stephanie J Chiu, Sina Farsiu, Donald O Mutti, Lisa A Jones-Jordan, Jeffrey J Walline","doi":"10.1167/iovs.66.5.5","DOIUrl":"https://doi.org/10.1167/iovs.66.5.5","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate changes in subfoveal choroidal thickness and area in children wearing soft multifocal contact lenses (MFCLs) for myopia control.</p><p><strong>Methods: </strong>Analyses included 281 myopic children aged 7 to 11 years in the Bifocal Lenses in Nearsighted Kids (BLINK) Study randomly assigned to wear single vision contact lenses (SVCLs), +1.50 D add, or +2.50 D add center-distance MFCL. Subfoveal choroidal thickness and choroidal area were measured using spectral-domain optical coherence tomography before and after 2 weeks of lens wear, and then annually for 3 years. Repeated measures linear regression was used to determine the effect of contact lens wear on the choroid and test the association between choroidal changes and axial elongation.</p><p><strong>Results: </strong>After initiating contact lens wear, mean ± SE subfoveal choroidal thickness and choroidal area increased in the +2.50 D MFCL group compared with the SVCL group by 8 ± 3 µm (P = 0.003) and 0.07 ± 0.02 mm2 (P = 0.002), a difference maintained throughout the 3-year study (P ≥ 0.55). Increased choroidal thickness and area after 2 weeks in the +2.50 D MFCL group vs. SVCL group were associated with less axial elongation over 3 years (β = -0.0058 mm/µm and -0.947 mm/mm2; P = 0.02 and P = 0.006; 20% and 29% of total treatment effect, respectively).</p><p><strong>Conclusions: </strong>The choroid increased in subfoveal thickness and area after 2 weeks of +2.50 D MFCL wear, which was maintained for 3 years and was associated with slower axial elongation. However, only a portion of the treatment effect can be accounted for by the choroidal parameters.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025011","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":"Chemokine System Changes Drive Age-Related Macular Degeneration and Influence Treatment Outcomes.","authors":"Alexander Kai Thomsen, Maria Abildgaard Steffensen, Amalie Thomsen Nielsen, Henrik Vorum, Bent Honoré, Mogens Holst Nissen, Torben Lykke Sørensen","doi":"10.1167/iovs.66.5.14","DOIUrl":"https://doi.org/10.1167/iovs.66.5.14","url":null,"abstract":"<p><strong>Purpose: </strong>The chemokine system is associated with age-related macular degeneration (AMD), shown in previous studies. In this study, we investigate these chemokines and chemokine receptors and their association with treatment response in neovascular AMD (nAMD), and association to intermediate AMD (iAMD).</p><p><strong>Methods: </strong>In this prospective cohort study, patients with nAMD, iAMD, and healthy controls were included. The initial and 1-year treatment response was evaluated in patients with nAMD. Plasma chemokine concentrations of CCL2, CCL3, CCL4, CCL20, CXCL8, and CXCL10 were measured with immunoassays. Chemokine receptor expression levels of CCR1, CCR2, CCR5, CCR6, CXCR2, CXCR3, and CX3CR1 on circulating T cells and monocytes were measured with flow cytometry. Correlation network analyses were performed of the chemokine system. Genotyping for CFH and ARMS2 risk polymorphisms was performed in patients with nAMD.</p><p><strong>Results: </strong>Patients with nAMD with poor initial treatment response had significantly lower proportions of CD4+CXCR3+, CCR5+ classical monocytes, and CCR2+ non-classical monocytes compared with good initial responders (all P < 0.05). Patients with nAMD with poor 1-year treatment response had significantly lower CD4+CXCR3+ and CCR2+ non-classical monocytes compared to good 1-year responders (both P < 0.05). Correlation networks revealed a more complex regulation in partial and poor initial treatment responders. Multiple chemokines and chemokine receptors significantly correlated with the risk genotypes of CFH and ARMS2.</p><p><strong>Conclusions: </strong>Patients with nAMD with poor treatment response had dysregulation of the chemokine system. The chemokine system might be a potential target of novel treatment in nAMD. Further studies are needed to clarify the chemokine system's role in nAMD treatment response.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 5","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012850","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}