Haiqi Xiao, Li Hu, Xiongshi Lin, Linchang Liu, Xing Dong, Liting Yang, Ying Liu, Zhichong Wang, Ying Tian, Shuangyong Wang
{"title":"Pax6 Directly Regulates the Raver2/sFlt-1 Expression in Corneal Epithelial Cells to Maintain the Cornea's Avascular Privilege.","authors":"Haiqi Xiao, Li Hu, Xiongshi Lin, Linchang Liu, Xing Dong, Liting Yang, Ying Liu, Zhichong Wang, Ying Tian, Shuangyong Wang","doi":"10.1167/iovs.66.4.52","DOIUrl":"https://doi.org/10.1167/iovs.66.4.52","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to elucidate how Pax6 directly regulates Raver2 and sFlt-1 expression in corneal epithelial cells to maintain the cornea's avascular privilege during normal development.</p><p><strong>Methods: </strong>The expression levels of Pax6, Raver2, and sFlt-1 in both the mouse cornea and human corneal epithelial cell line (HCE-T) were evaluated. Changes in Raver2 and sFlt-1 expression following Pax6 knockdown were also assessed. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR), electrophoresis mobility shift assay (EMSA), and dual-luciferase reporter (DLR) assay were conducted to ascertain the regulatory relationship between Pax6 and Raver2. The impact on vascular endothelial cell proliferation, migration, and tube formation was examined after coculturing with siPax6-HCE-T conditioned culture medium. Additionally, corneal neovascularization (CoNV) was monitored following corneal epithelial scraping or injection of the AAV-siPax6 vector into the limbus.</p><p><strong>Results: </strong>Pax6, Raver2, and sFlt-1 were highly expressed in both HCE-T cells and normal mouse corneal epithelial layer. Interference with Pax6 expression resulted in decreased levels of Raver2 and sFlt-1 both in vivo and in vitro. TFBS1 and TFBS2 in the Raver2 promoter region were identified as potential Pax6 binding sites. ChIP-qPCR and EMSA assays confirmed the direct interaction between Pax6 and Raver2. The DLR assay demonstrated that Pax6 binding to the TFBS1 and TFBS2 regulated Raver2 expression. Vascular endothelial cell proliferation, migration, and tube formation were enhanced when cocultured with siPax6-HCE-T conditioned culture medium. CoNV progressed after corneal epithelial scraping and AAV-siPax6 vector injection.</p><p><strong>Conclusions: </strong>Pax6 directly regulates Raver2/sFlt-1 expression in corneal epithelial cells, thus preserving the cornea's avascular privilege during normal development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"52"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003340","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}
Sebastiano Giallongo, Francesco Bellia, Andrea Russo, Matteo Fallico, Riccardo Polosa, Niccolò Castellino, Antonio Longo, Rosalia Emma, Konstantinos Partsinevelos, Massimo Caruso, Arief S Kartasasmita, Giuseppe Sferrazzo, Ignazio Alberto Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Amer M Alanazi, Giovanni Li Volti
{"title":"Comparative Evaluation of Cigarette Smoke and a Heated Tobacco Product on Corneal Oxidative Stress in an Air/Liquid Interface Model.","authors":"Sebastiano Giallongo, Francesco Bellia, Andrea Russo, Matteo Fallico, Riccardo Polosa, Niccolò Castellino, Antonio Longo, Rosalia Emma, Konstantinos Partsinevelos, Massimo Caruso, Arief S Kartasasmita, Giuseppe Sferrazzo, Ignazio Alberto Barbagallo, Rosario Caltabiano, Giuseppe Broggi, Amer M Alanazi, Giovanni Li Volti","doi":"10.1167/iovs.66.4.4","DOIUrl":"10.1167/iovs.66.4.4","url":null,"abstract":"<p><strong>Purpose: </strong>Tobacco smoke harbors toxic combustion by-products contributing to inflammatory diseases. Cigarette smoke's impact on ocular diseases has been poorly characterized, despite conjunctival mucosa's sensitivity to these toxicants. Of note, cigarette smoke triggers redness, tearing, and discomfort, accounting as a risk factor for glaucoma, macular degeneration, cataracts, and other eye conditions. Low quit rates of cessation highlight the need for alternatives. Heated tobacco products (HTPs), may represent a less toxic alternative for those smokers. This study evaluates cigarette smoke and HTPs effects on cornea under standard and clinically relevant conditions.</p><p><strong>Methods: </strong>Corneal tissues collected from donors and in vitro model in two different cell lines of corneal epithelium were exposed to cigarette (1R6F) smoke and HTPs vapor. Air exposure was included as a control. Tissue pathological evaluation was carried out by hematoxylin and eosin staining. Reactive oxygen species (ROS) were measured, and quantitative PCR assessed inflammatory and antioxidant genes expression. Proteome analysis was used to evaluate differentially expressed proteins related to the oxidative stress. Scratch assay measured smoke and HTPs impact on cells.</p><p><strong>Results: </strong>Hematoxylin & eosin staining highlighted that cigarette smoke impairs corneal tissue integrity, leading to ROS accumulation and inflammation, as proved by qPCR analysis. Proteomic analysis showed that corneal tissue's proteins were differently oxidized by the different experimental conditions. HTP targeted structural intracellular proteins, whereas 1R6F affects different members of collagen family. Finally, cigarette smoke, but not HTPs, impairs epithelial cells wound closure.</p><p><strong>Conclusions: </strong>Smoking increases oxidative stress, leading to significant corneal damage and inflammation. HTPs may offer a less toxic alternative.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763952","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}
Caili Hao, Emily Fan, Zongbo Wei, Kazi Rafsan Radeen, Neha Purohit, Kailin Li, Sharad Purohit, Xingjun Fan
{"title":"Elevated Inflammatory Cytokines Persist in the Aqueous Humor Years After Cataract Surgery.","authors":"Caili Hao, Emily Fan, Zongbo Wei, Kazi Rafsan Radeen, Neha Purohit, Kailin Li, Sharad Purohit, Xingjun Fan","doi":"10.1167/iovs.66.4.12","DOIUrl":"10.1167/iovs.66.4.12","url":null,"abstract":"<p><strong>Purpose: </strong>There is currently limited information regarding inflammation and cytokine levels in the aqueous humor (AH) of adult patients with cataract who have undergone phacoemulsification cataract extraction without other ocular comorbidities.</p><p><strong>Methods: </strong>AH samples were collected from healthy, non-surgical donors and donors with a history of cataract surgery performed 3 to 12 years prior. Sixty-three cytokines and growth factors were measured using bead-based ProcartaPlex immunoassays. Data analysis included normal distribution assessment, pairwise correlation, logistic regression, and ridge regression.</p><p><strong>Results: </strong>Of the 63 molecules analyzed, 34 were selected for further study. Cytokines, such as CD40L, IL-7, MIP-1α, and LIF, were found at significantly higher concentrations in AH samples from donors with a history of cataract surgery compared with non-cataract controls. In contrast, lower concentrations of IL-23, TRAIL, IL-12p70, IFNγ, MIP-3α, and SCF were observed in post-surgical samples. Pairwise correlation analysis identified clusters of significantly correlated molecules, suggesting their potential involvement in the inflammatory environment of AH post-cataract surgery. AH concentration of 34 proteins was combined into a post-cataract surgery inflammation index (PCSII) using ridge regression, which differs significantly between post-cataract surgery donors and non-cataract controls. This PCSII shows that any increase in AH levels of these molecules can stratify cataract surgery donors into low and high-risk of inflammatory groups.</p><p><strong>Conclusions: </strong>This study indicates that cataract surgery may lead to a chronic inflammatory state in the AH, which can persist for extended periods post-surgery.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780013","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":"Antigen Presentation by Extracellular Vesicles in the Acute Phase of Corneal Transplantation.","authors":"Toshiki Shimizu, Takahiko Hayashi, Junki Kurita, Kentaro Yuda, Nobuhisa Mizuki, Satoru Yamagami","doi":"10.1167/iovs.66.4.38","DOIUrl":"https://doi.org/10.1167/iovs.66.4.38","url":null,"abstract":"<p><strong>Purpose: </strong>Corneal transplantation is the most frequently performed solid organ transplantation procedure worldwide. We aimed to investigate the role of extracellular vesicles in allorecognition and the rejection of allografts in corneal transplantation using male C57BL/6 (B6 and IAb) and BALB/c (IAd) mice.</p><p><strong>Methods: </strong>The mice were aged 8 to 12 weeks. We used transmission electron microscopy to visualize the drainage of extracellular vesicles derived from the graft into the cervical lymph nodes using gold colloids as markers in a mouse model of corneal transplantation.</p><p><strong>Results: </strong>Lymph node cells sensitized to graft-derived extracellular vesicles exhibited high proliferation when exposed to cultured corneal stromal cells in a mixed lymphocyte reaction. Notably, extracellular vesicles carrying graft-derived IA antigens were detected in cervical lymph nodes within a maximum of 6 hours postoperatively. Moreover, the administration of extracellular vesicles extracted from cultured corneal stromal cells significantly reduced the graft survival rate.</p><p><strong>Conclusions: </strong>These findings provide the first evidence of a semi-direct pathway in which graft-derived extracellular vesicles are captured in cervical lymph nodes and contribute to the promotion of allograft rejection in corneal transplantation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"38"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024176","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}
Yuzhou Wang, Zhiqiang Xu, Linzhi Wei, Yang Lu, Yizhou Shi, Shiyu Wen, Xiujuan Lv, Kaiyan Huang, Fan Lu, Jia Qu, Liang Hu
{"title":"KGF-2 Alleviates Dry Eye Disease by Regulating the HMGB1/TLR4 Pathway.","authors":"Yuzhou Wang, Zhiqiang Xu, Linzhi Wei, Yang Lu, Yizhou Shi, Shiyu Wen, Xiujuan Lv, Kaiyan Huang, Fan Lu, Jia Qu, Liang Hu","doi":"10.1167/iovs.66.4.28","DOIUrl":"https://doi.org/10.1167/iovs.66.4.28","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the protective effects of keratinocyte growth factor-2 (KGF-2) in dry eye disease (DED) and elucidate its mechanism of action through the regulation of the HMGB1/TLR4 pathway.</p><p><strong>Methods: </strong>Two in vitro models were established by stimulating hyperosmolar human corneal epithelial cells (HCECs) and RAW 264.7 cells with lipopolysaccharide. A DED mice model was established using scopolamine and an intelligently controlled environmental system. After KGF-2 treatment, the symptoms of the DED mice were assessed. The changes in inflammatory factors were measured using Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR). RNA sequencing (RNA-seq) was used to identify the key factors involved in KGF-2 treatment, followed by validation through in vivo and in vitro knockdown of the relevant factors.</p><p><strong>Results: </strong>KGF-2 treatment significantly relieved DED in the mice model through increased tear secretion, and improved fluorescein staining scores. In addition, the levels of inflammatory factors were effectively lowered in both in vitro and in vivo models. Bulk RNA-seq analysis suggested that KGF-2 exerts its effects by regulating the HMGB1/TLR4 pathway. Furthermore, KGF-2 treatment inhibited the upregulation and nuclear translocation of HMGB1 in the DED model, thereby suppressing the levels of inflammatory factors associated with the HMGB1/TLR4 pathway. Knockdown of HMGB1 in HCECs and glycyrrhizin treatment in DED mice exhibited therapeutic effects similar to those of KGF-2.</p><p><strong>Conclusions: </strong>KGF-2 demonstrated protective effects in both in vivo and in vitro DED models by modulating the HMGB1/TLR4 pathway. These findings suggest its potential as a therapeutic agent for DED, warranting further clinical investigation in this regard.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035322","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}
Danny Toribio, Junji Morokuma, Dante Pellino, Markus Hardt, Driss Zoukhri
{"title":"Quantitative Changes in the Proteome of Chronically Inflamed Lacrimal Glands From a Sjögren's Disease Animal Model.","authors":"Danny Toribio, Junji Morokuma, Dante Pellino, Markus Hardt, Driss Zoukhri","doi":"10.1167/iovs.66.4.44","DOIUrl":"https://doi.org/10.1167/iovs.66.4.44","url":null,"abstract":"<p><strong>Purpose: </strong>The lacrimal gland (LG) is the major source of aqueous tears, and insufficient LG secretion leads to aqueous-deficient dry eye (ADDE) disease. To provide a foundational description of LG's protein expression patterns, we prepared protein extracts of LGs from a wild-type and an ADDE mouse model and analyzed the proteome by quantitative mass spectrometry.</p><p><strong>Methods: </strong>LGs were isolated from an ADDE mouse model, male non-obese diabetic (NOD) mice and control wild-type BALB/c mice (n = 6 each). Protein samples were prepared in urea-based lysis buffer and protein concentrations determined by the BCA method. The equivalent of 200 µg protein were tryptically digested and analyzed by nanoflow liquid chromatography tandem mass spectrometry (LC-MS/MS). Proteins were identified and quantified using the PEAKS X bioinformatics suite. Downstream differential protein expression analysis was performed using the MS-DAP R package. Selected significantly differentially expressed and detected proteins were subjected to spatial expression analysis using immunohistochemistry.</p><p><strong>Results: </strong>Cumulatively, the LC-MS/MS-based proteomics analyses of the murine LG samples identified a total of 31,932 peptide sequences resulting in 2617 protein identifications at a 1% false discovery rate at the peptide and protein level. Principal component analysis (PCA) and hierarchical cluster analysis revealed a separation of NOD and BALB/c samples. Overall, protein diversity was consistently higher in NOD samples. After applying global peptide filter criteria and peptide-to-protein rollup, 1750 remaining proteins were subjected to differential expression analysis using the MSqRob algorithm, which identified 580 proteins with statistically significant expression differences. Data are available via ProteomeXchange with identifier PXD060937. At the cellular level, the up- and downregulation of select proteins were confirmed by immunohistochemistry.</p><p><strong>Conclusions: </strong>Our data suggest that chronic inflammation leads to significant alterations in the LG proteome. Ongoing studies aim to identify potentially unique, inflammation-induced proteins that could be amenable to pharmacological modulation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"44"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990594","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}
Lorenzo Bianco, Alessio Antropoli, Amine Benadji, Raphaël Atia, Oana Palacci, Christel Condroyer, Aline Antonio, Julien Navarro, Maurizio Battaglia Parodi, José-Alain Sahel, Christina Zeitz, Isabelle Audo
{"title":"PCARE-Associated Retinopathy - Genetics, Clinical Characteristics, and Natural History.","authors":"Lorenzo Bianco, Alessio Antropoli, Amine Benadji, Raphaël Atia, Oana Palacci, Christel Condroyer, Aline Antonio, Julien Navarro, Maurizio Battaglia Parodi, José-Alain Sahel, Christina Zeitz, Isabelle Audo","doi":"10.1167/iovs.66.4.61","DOIUrl":"https://doi.org/10.1167/iovs.66.4.61","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to describe the mutational landscape, clinical characteristics, and natural history of PCARE-associated retinopathy.</p><p><strong>Methods: </strong>Retrospective cohort study including 28 patients (56 eyes) affected by an inherited retinal disease related to PCARE variants. The main outcome measures were best-corrected visual acuity (BCVA) and degree of vision impairment, kinetic visual field (KVF) area delimited with the V4e target, area of macular atrophy (MA) with definitely decreased autofluorescence (DDAF) on short-wavelength autofluorescence, total macular volume (TMV) and foveal sparing (FS) on optical coherence tomography.</p><p><strong>Results: </strong>The median age at first examination was 40.7 years (Interquartile range [IQR] = 28.8-49.6), whereas the median follow-up time was 5.7 years (IQR = 3.6-7.1). The retinal phenotype was consistent with a severe generalized photoreceptor dystrophy with MA in all patients. DDAF lesions were observed in 85% of the eyes. Loss of FS (occurring at a median age of 45 years) was associated with a mean BCVA (logMAR) worsening by 1.1 (95% confidence interval [CI] = 0.6 to 1.5, P < 0.001). Low vision and blindness in the better-seeing eye occurred at median ages of 50 and 57 years, respectively. Longitudinal analysis revealed the following mean slopes of change: BCVA (logMAR) worsened by 0.06/year (95% CI = 0.03 to 0.09, P < 0.001), KVF area decreased by -23%/year (95% CI = -35% to -12%, P = 0.004), square root-transformed DDAF area expanded by 0.20 mm/year (95% CI = 0.16 to 0.23, P < 0.001), and TMV declined by -0.015 mm3/year (95% CI = -0.023 to -0.007, P = 0.003). Eleven novel PCARE variants were identified.</p><p><strong>Conclusions: </strong>PCARE-associated retinopathy is a severe generalized photoreceptor dystrophy with MA. Although visual field loss occurs early, useful central vision is often retained into late adulthood because of FS. Based on the age of onset of legal blindness, the optimal therapeutic window appears to be before the fifth decade of life.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"61"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965180","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":"Macrophage-Hosted Porphyromonas gingivalis Is a Risk Factor for Cataract Development.","authors":"Dongzhe Zhang, Junwei Qu, Cuncun Ke, Xiumei Kong, Mengyun Liu, Iqbal Nawaz Khan, Shuxin Huang, Haijiao Tian, Tong Xie, Ke Qiu, Jing Li, Mingli Wang, Hui Li, Fengling Yuan, Weikai Guo, Mingya Cao, Jing Zhang, Keke Zhu, Jin Luo, Fengyan Zhang, Xiukun Cui, Hongmei Mu, Yanzhong Hu","doi":"10.1167/iovs.66.4.68","DOIUrl":"https://doi.org/10.1167/iovs.66.4.68","url":null,"abstract":"<p><strong>Purpose: </strong>We studied the regulatory association of Porphyromonas gingivalis (PG) and cataracts.</p><p><strong>Methods: </strong>PCR and FISH assays were used for detecting PG 16s ribosomal RNA genome, Immunofluorescence was for expression of RpgA in anterior capsular epithelium and fibrosis markers in anterior subcapsular cataract (ASC) model. Flow cytometry was for reactive oxygen species and apoptosis. RNA deep sequencing is for differential gene expression analysis.</p><p><strong>Results: </strong>PG's 16s ribosomal RNA gene is positively in 43.3% (101/233 cases) of aqueous humor (AH) samples of patients with cataracts, which differs from 4.7% (6/127) of PG-positive AH in patients with glaucoma. Diabetic and high myopia cataracts increase PG-positive AH compared with age-related cataracts. No PG is observed in AH of congenital cataracts. PG is positive in 82% to 94% of the cataractous anterior capsule tissues from high myopia and age-related, congenital, and diabetic cataracts. The PG-positive cells in the cataractous anterior capsular epithelium are CD68+/CD14+ macrophages, but not anterior epithelial cells. In rat ASC models, PG injected via the tail vein or PG-carried bone marrow monocytes can migrate into the equatorial lens epithelium in form of PG-positive macrophages, which promote ASC progression with upregulation of collagen, fibronectin and α smooth muscle actin (α-SMA) expression, and increase 8-OHdG levels and α-SMA expression in the surrounding lens epithelial cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis of the RNA sequencing dataset of ASC tissues shows that signaling pathways related to epithelial-mesenchymal transition, oxidative stress, and cell death are up-regulated in PG + ASC compared with that in ASC alone. Co-culture of supernatants of Raw264.7/PG+ cells with rat primary lens epithelial cells increases the 8-OHdG levels, mitochondrial fission, apoptosis, and expression of α-SMA.</p><p><strong>Conclusions: </strong>Chronic infection with PG can access the lens epithelium via macrophages during stress conditions, which promotes cataract development by possibly elevating oxidative stress, apoptosis, and epithelial-mesenchymal transition in lens tissues. PG infection is a novel a risk factor for cataract development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"68"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981207","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}
Zi Xuan Lin, Xiu Juan Zhang, Fang Yao Tang, Yuzhou Zhang, Ka Wai Kam, Alvin L Young, Patrick Ip, Carol Y Cheung, Chi Pui Pang, Clement C Tham, Li Jia Chen, Kyoko Ohno-Matsui, Jason C Yam
{"title":"Association of Retinal Microvasculature With Myopia Progression in Children: The Hong Kong Children Eye Study.","authors":"Zi Xuan Lin, Xiu Juan Zhang, Fang Yao Tang, Yuzhou Zhang, Ka Wai Kam, Alvin L Young, Patrick Ip, Carol Y Cheung, Chi Pui Pang, Clement C Tham, Li Jia Chen, Kyoko Ohno-Matsui, Jason C Yam","doi":"10.1167/iovs.66.4.64","DOIUrl":"https://doi.org/10.1167/iovs.66.4.64","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the associations between optical coherence tomography angiography (OCT-A) metrics and myopia progression in children.</p><p><strong>Methods: </strong>This prospective, longitudinal cohort study recruited children ages 6 to 8 years for 2- to 6-year follow-ups. OCT-A captured macular images from the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Annual progression of spherical equivalent (SE) and axial length (AL) was calculated as (SE/AL at last visit - SE/AL at baseline)/follow-up duration. Multivariable linear regression analysis evaluated the associations of OCT-A metrics with SE/AL progression. Restricted cubic spline (RCS) analysis evaluated both linear and nonlinear associations. Holm-Bonferroni correction was applied to account for multiple comparisons.</p><p><strong>Results: </strong>A total of 920 children were analyzed. Multivariable linear regression, adjusted for age, sex, baseline SE/AL, and other covariates, showed that baseline foveal avascular zone (FAZ) circularity was negatively associated with annual AL elongation (β = -0.06; 95% confidence interval [CI], -0.10 to -0.02; adjusted P = 0.045). Similarly, the baseline FAZ circularity was positively associated with annual SE progression (β = 0.15; 95% CI, 0.05-0.26; adjusted P = 0.045). No significant associations were found between OCT-A metrics in the DCP with annual AL/SE progression. Furthermore, RCS analysis demonstrated no significant nonlinear associations between OCT-A metrics and annual AL/SE progression (P for nonlinearity > 0.05).</p><p><strong>Conclusions: </strong>Baseline FAZ circularity in the SCP was significantly associated with annual AL elongation and annual SE progression in children, suggesting its potential as an imaging biomarker for monitoring myopia progression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"64"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966569","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}
Yu Peng, Yuzhou Zhang, Ka Wai Kam, Gavin Wong, Mary Ho, Simon Sezto, Sunny Au, Xiujuan Zhang, Mandy P H Ng, Patrick Ip, Alvin Young, Chi Pui Pang, Clement C Tham, Li Jia Chen, Jason C Yam
{"title":"Associations of Cardiovascular Health and New-Onset Age-Related Macular Diseases From UK Biobank.","authors":"Yu Peng, Yuzhou Zhang, Ka Wai Kam, Gavin Wong, Mary Ho, Simon Sezto, Sunny Au, Xiujuan Zhang, Mandy P H Ng, Patrick Ip, Alvin Young, Chi Pui Pang, Clement C Tham, Li Jia Chen, Jason C Yam","doi":"10.1167/iovs.66.4.63","DOIUrl":"https://doi.org/10.1167/iovs.66.4.63","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the correlation between cardiovascular health (CVH), evaluated through the Life's Essential 8 (LE8) score, and the risk of new-onset age-related macular degeneration (AMD).</p><p><strong>Methods: </strong>This longitudinal analysis included 271,274 participants who were free of both cardiovascular diseases and AMD at baseline. The LE8 score was classified into three categories: low (<50 points), moderate (50 to <80 points), and high (≥80 points), with higher scores indicating better CVH. Cox proportional hazards models were used to explore the relationships between the CVH and AMD incidence. Furthermore, the population attributable risk (PAR%) was calculated for CVH and each individual metric.</p><p><strong>Results: </strong>During an average follow-up duration of 10.9 years, a total of 7468 (2.8%) cases of AMD were documented. Individuals with moderate and high CVH levels had a 14% (hazard ratio [HR] = 0.86; 95% confidence interval [CI], 0.78-0.94) and 23% (HR = 0.77; 95% CI, 0.69-0.86) reduced risk of developing AMD, respectively. A linear dose-response relationship was identified between the cumulative LE8 score and the incidence of AMD. Attaining optimal CVH in all individuals could potentially avert 9.4% (95% CI, 3.7%-15.1%) of AMD cases. Among the CVH metrics, ideal blood glucose and blood pressure levels were related to a reduction of 3.3% and 8.7% in AMD cases, respectively.</p><p><strong>Conclusions: </strong>Enhanced CVH is significantly associated with a reduced risk of developing AMD. Promoting CVH through the LE8 guideline might potentially contribute to the prevention of AMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"63"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012779","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}