Investigative ophthalmology & visual science最新文献

{"title":"Erratum in: TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism.","authors":"","doi":"10.1167/iovs.65.13.20","DOIUrl":"10.1167/iovs.65.13.20","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620760","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":"Treatment of Conjunctival Melanoma Cell Lines With a Light-Activated Virus-Like Drug Conjugate Induces Immunogenic Cell Death.","authors":"Sen Ma, Ruben V Huis In't Veld, Elisabet de Los Pinos, Ferry A Ossendorp, Martine J Jager","doi":"10.1167/iovs.65.13.3","DOIUrl":"10.1167/iovs.65.13.3","url":null,"abstract":"<p><strong>Purpose: </strong>Conjunctival melanoma (CJM) is a rare malignant ocular surface tumor, which often leads to local recurrences and metastases. In murine models of subcutaneous tumors, treatment with a novel virus-like drug conjugate (VDC; Bel-sar) showed a dual mechanism of action with direct tumor cell killing as well as stimulation of an antitumoral immune response. Bel-sar is currently being evaluated for the treatment of primary uveal melanoma and indeterminate nevi in a phase III clinical trial. We determined whether Bel-sar also has direct antitumor efficiency and a potential immunostimulatory capacity in CJM cells.</p><p><strong>Methods: </strong>Three human tumor-derived CJM lines were used. Bel-sar's subcellular and intracellular locations were determined with tracers. Following light activation of Bel-sar, cytotoxicity and exposure of damage-associated molecular patterns (DAMPs) were assessed. Treated tumor cells were co-cultured with THP-1 derived macrophages to assess tumor-cell phagocytosis.</p><p><strong>Results: </strong>Bel-sar was bound and internalized by CJM cells and subsequently found in the cell membrane, lysosome, Golgi apparatus, and mitochondria. Bel-sar activation induced near complete cell death with half-maximal inhibitory concentration (IC50) values between 30 pM and 60 pM. Finally, light-activated Bel-sar enhanced exposure of DAMPs, including calreticulin, heat shock protein 90, and stimulated phagocytosis by macrophages.</p><p><strong>Conclusions: </strong>Treatment with a novel VDC (Bel-sar) induced pro-immunogenic cell death in all three CJM cell lines. The in vitro cytotoxicity was accompanied by exposure of DAMPs, suggesting Bel-sar is a potential treatment for CJM by a dual mechanism of action. This dual mechanism may provide a targeted and direct killing of tumor cells and induce an immune response which might decrease local recurrences and metastasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568644","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":"VEP Latency Delay Reflects Demyelination Beyond the Optic Nerve in the Cuprizone Model.","authors":"Roshana Vander Wall, Devaraj Basavarajappa, Viswanthram Palanivel, Samridhi Sharma, Vivek Gupta, Alexander Klistoner, Stuart Graham, Yuyi You","doi":"10.1167/iovs.65.13.50","DOIUrl":"10.1167/iovs.65.13.50","url":null,"abstract":"<p><strong>Purpose: </strong>Remyelination therapies are advancing for multiple sclerosis, focusing on visual pathways and using visual evoked potentials (VEPs) for de/remyelination processes. While the cuprizone (CZ) model and VEPs are core tools in preclinical trials, many overlook the posterior visual pathway. This study aimed to assess functional and structural changes across the murine visual pathway during de/remyelination.</p><p><strong>Methods: </strong>One group of C57BL/6 mice underwent a CZ diet for 6 weeks to simulate demyelination, with a subset returning to a regular diet to induce remyelination. An additional group was fed a protracted CZ diet for 12 weeks to maintain chronic demyelination. Visual function was evaluated using electrophysiological recordings, including scotopic threshold responses (STRs) and electroretinograms (ERGs), with VEPs serving as a key biomarker for overall pathway health. Tissues from eyes, brains, and optic nerves (ONs) were collected at different time points for structural analysis.</p><p><strong>Results: </strong>Our results demonstrated significant effects on VEPs, including increased N1 latencies and reduced amplitudes in the CZ mouse model. However, retinal function remained unaffected, as evidenced by unchanged STRs, ERGs, and retinal ganglion cell counts. Analysis of ONs revealed morphological changes, characterized by a significantly decreased axon diameter in the core region compared to the subpial region. Additionally, there was a significant increase in the g-ratio of the core region at 12 weeks CZ compared to controls. Immunofluorescence further demonstrated a decrease in myelin basic protein levels at 6 and 12 weeks in CZ animals. Interestingly, the dorsal lateral geniculate nucleus and primary visual cortex (V1) exhibited similar myelin changes, correlating with VEP latency alterations.</p><p><strong>Conclusions: </strong>These data reveal that interpreting VEP latency solely as a marker for ON demyelination is incomplete. Previous preclinical studies have overlooked the posterior visual pathways, necessitating a broader interpretation of VEP latency to cover the entire visual pathway.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"50"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686986","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":"Blind But Alive - Congenital Loss of atoh7 Disrupts the Visual System of Adult Zebrafish.","authors":"Juliane Hammer, Paul Röppenack, Sarah Yousuf, Anja Machate, Marika Fischer, Stefan Hans, Michael Brand","doi":"10.1167/iovs.65.13.42","DOIUrl":"10.1167/iovs.65.13.42","url":null,"abstract":"<p><strong>Purpose: </strong>Vision is the predominant sense in most animal species. Loss of vision can be caused by a multitude of factors resulting in anatomic as well as behavioral changes. In mice and zebrafish, atoh7 mutants are completely blind as they fail to generate retinal ganglion cells (RGCs) during development. In contrast to mice, raising blind zebrafish to adulthood is challenging and this important model is currently missing in the field. Here, we report the phenotype of homozygous mutant adult zebrafish atoh7 mutants that have been raised using adjusted feeding and holding conditions.</p><p><strong>Methods: </strong>The phenotype of adult mutants was characterized using classical histology and immunohistochemistry as well as optical coherence tomography. In addition, the optokinetic response was characterized.</p><p><strong>Results: </strong>Adult atoh7 mutants display dark body pigmentation and significantly reduced body length. They fail to form RGCs, the resulting nerve fiber layer as well as the optic nerve, and consequently behave completely blindly. In contrast, increased amounts of other retinal neurons and Müller glia are formed. In addition, the optic tectum is anatomically reduced in size, presumably due to the missing retinal input.</p><p><strong>Conclusions: </strong>Taken together, we provide a comprehensive characterization of a completely blind adult zebrafish mutant with focus on retinal and tectal morphology, as a useful model for glaucoma and optic nerve aplasia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"42"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675762","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":"Retinal Function in Advanced Multiple Sclerosis.","authors":"James V M Hanson, Sara Single, Rahel B Eberle, Veronika Kana, Benjamin V Ineichen, Christina Gerth-Kahlert","doi":"10.1167/iovs.65.13.2","DOIUrl":"10.1167/iovs.65.13.2","url":null,"abstract":"<p><strong>Purpose: </strong>People with multiple sclerosis (pwMS) experience autoimmunity-mediated inflammation and neurodegeneration throughout the central nervous system. There remains a need for clinically accessible, reliable functional markers of neurodegeneration in MS. Previous research has described changes to electroretinography (ERG)-derived measures of retinal bipolar cell function in pwMS early in the disease course. We, therefore, investigated ERG as a potential outcome measure in individuals with more advanced disease.</p><p><strong>Methods: </strong>This cross-sectional observational study included pwMS with Expanded Disability Status Scale (EDSS) scores of ≥3.0 and healthy control (HC) participants who underwent ERG, optical coherence tomography, high- and low-contrast visual acuity measurement, and an ophthalmological examination. ERG findings in MS eyes with and without previous optic neuritis (MS +ON; MS -ON) were compared with those in HC eyes. Effects of EDSS, disease duration, ON, and treatment status on selected ERG outcomes were measured. Additional exploratory analyses assessed potential influences of MS phenotype and disease status (clinically active, radiologically active, and disease progression).</p><p><strong>Results: </strong>Delays to two ERG peak times (dark-adapted 3.0 b-wave; light-adapted flicker) were recorded in MS +ON and MS -ON eyes. No influences of EDSS score, disease duration, previous ON, or treatment status were observed. Exploratory analyses were consistent with no effects of MS phenotype or disease status.</p><p><strong>Conclusions: </strong>ERG findings are abnormal in individuals with moderate-severe disability caused by MS; however, these findings are not distinct from those observed earlier in the disease course. Although bipolar dysfunction appears to be common in pwMS throughout the disease course, ERG is likely not useful in monitoring or prognostication of MS.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568642","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":"Mechanisms Regulating Mitochondrial Transfer in Human Corneal Epithelial Cells.","authors":"Sonali Pal-Ghosh, Beverly A Karpinski, Himani Datta-Majumdar, Soneha Datta, Shelly Dimri, Jordan Hally, Hugo Wehmeyer, Mary Ann Stepp","doi":"10.1167/iovs.65.13.10","DOIUrl":"10.1167/iovs.65.13.10","url":null,"abstract":"<p><strong>Purpose: </strong>The intraepithelial corneal nerves (ICNs) innervating the cornea are essential to corneal epithelial cell homeostasis. Rho-associated kinase (ROCK) inhibitors (RIs) have been reported to play roles in neuron survival after injury and in mitochondrial transfer between corneal epithelial cells. In this study, the mechanisms human corneal limbal epithelial (HCLE) cells use to control intercellular mitochondrial transfer are assessed.</p><p><strong>Methods: </strong>Mitotracker and AAV1 mitotag eGFPmCherry were used to allow us to study mitochondrial transfer between HCLE cells and neurons in co-cultures and in HCLE cultures. A mitochondrial transfer assay was developed using HCLE cells to quantify the impact of cell stress and inhibition of phagocytosis, gap junctions, and ROCK on mitochondrial transfer, cell adhesion, migration, matrix deposition, and mitochondrial content.</p><p><strong>Results: </strong>Bidirectional mitochondrial transfer occurs between HCLE cells and neurons. Mitochondrial transfer among HCLE cells is inhibited when gap junction function is reduced and enhanced by acid stress and by inhibition of either phagocytosis or ROCK. Media conditioned by RI-treated cells stimulates cell adhesion and mitochondrial transfer.</p><p><strong>Conclusions: </strong>Maximal mitochondrial transfer takes place when gap junctions are functional, when ROCK and phagocytosis are inhibited, and when cells are stressed by low pH media. Treatments that reduce mitochondrial content increase HCLE cell mitochondrial transfer. ROCK inhibition in co-cultures causes the release and adhesion of mitochondria to substrates where they can be engulfed by migrating HCLE cells and growing axons and their growth cones.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583013","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":"Investigating Microperimetric Features in Bietti Crystalline Dystrophy Patients: A Cross-Sectional Longitudinal Study in a Large Cohort.","authors":"Yufei Xu, Xiao Liu, Nan Wu, Yanling Long, Jiayun Ren, Yu Wang, Xinyi Su, Zengping Liu, Yu Fujinami-Yokokawa, Kaoru Fujinami, Fang Chen, Xiaohong Meng, Yong Liu","doi":"10.1167/iovs.65.13.27","DOIUrl":"10.1167/iovs.65.13.27","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the clinical and genetic characteristics of patients with Bietti crystalline dystrophy (BCD) with a focus on potential of microperimetry in monitoring macular function.</p><p><strong>Methods: </strong>A total of 208 genetically-confirmed BCD patients were enrolled in this retrospective study. The patients were categorized into subgroups based on their fundus characteristics (fovea sparing and fovea involved), optical coherence tomography (OCT) findings (presence/absence of retinal pigment epithelium [RPE] or ellipsoid zone [EZ] line at the fovea/parafovea), and genetic profiles (Mis/Mis, Tru/Mis, Tru/Tru). Fixation patterns were analyzed, and macular sensitivity (MS) parameters were compared among different groups. Longitudinal analysis was performed to calculate the annual changes in MS parameters. Correlation between genotype and phenotype were further investigated by analyzing cumulative incidence of vision impairment among different genotypic groups.</p><p><strong>Results: </strong>Patients with well-preserved RPE or EZ at the foveal/parafoveal region exhibited higher MS. Notably, there was a decline in sensitivity parameters, with a decrease of -2.193 dB/year (95% confidence interval [CI] -4.292 to -0.095, P = 0.041) at the fovea and -1.353 dB/year (95% CI -2.047 to -0.659, P < 0.001) in average sensitivity. An age-adjusted comparison of sensitivity among genotypic groups and cumulative incidence analyses showed no association between genotypic groups and vision loss.</p><p><strong>Conclusions: </strong>Microperimetry proves to be one of a credible tool for detecting macular functional changes in BCD patients. BCD patients with different genotypes may have similar disease progression.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620773","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 and Rapid In Vivo Imaging of Human Lenticular Fluorescence.","authors":"Joshua M Herzog, Angela Verkade, Volker Sick","doi":"10.1167/iovs.65.13.41","DOIUrl":"https://doi.org/10.1167/iovs.65.13.41","url":null,"abstract":"<p><strong>Purpose: </strong>To quantitatively investigate the chemical origins of near-UV excited fluorescence in the crystalline lens, and demonstrate the potential usefulness of a rapid and noninvasive diagnostic approach for screening and monitoring of lens damage.</p><p><strong>Methods: </strong>Anterior segment UV fluorescence imaging was applied to a population of 30 healthy adults, ages 18 to 64 years. Absolute fluorescence intensities and intensity ratios were compared across the population as a function of age. Fluorescence quantum yield (FQY) was calculated from imaging results based on a previous radiometric characterization.</p><p><strong>Results: </strong>Typical FQYs at 365 nm excitation are approximately 0.2% for healthy adults. Intensity and FQY were observed to increase significantly with age, consistent with ex vivo and confocal microscopy studies. The ratio of blue to green fluorescence is strongly correlated with FQY and age, suggesting that both increases in fluorophore concentration and changes in composition occur with age. Fluorescence data is quantitatively and qualitatively consistent with pyridine nucleotides in young adults, and changes with age are consistent with formation of β-carbolines or advanced glycation end products. Intralens variation is consistent with increased oxidation or glycation in the lens nucleus relative to the cortex.</p><p><strong>Conclusions: </strong>Lenticular fluorescence can be measured rapidly, accurately, and quantitatively in vivo which provides a spatially resolved, quantitative measure of lens chemistry, including damage from oxidation and glycation. Careful interpretation of fluorescence intensities and intensity ratios can provide chemical insight into lens health. Anterior segment UV fluorescence imaging can thus serve as a useful tool for screening, monitoring, and research of lens damage and cataract formation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"41"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675765","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":"Three-Dimensional Choroidal Vessels Assessment in Age-Related Macular Degeneration.","authors":"Elham Sadeghi, Nicola Valsecchi, Mohammed Nasar Ibrahim, Katherine Du, Elli Davis, Sandeep Chandra Bollepalli, Kiran Kumar Vupparaboina, Jose Alain Sahel, Jay Chhablani","doi":"10.1167/iovs.65.13.39","DOIUrl":"10.1167/iovs.65.13.39","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the choroidal vasculature in eyes with early- and intermediate-stage age-related macular degeneration (dAMD) and healthy using a novel three-dimensional algorithm.</p><p><strong>Methods: </strong>Patients with dAMD and healthy controls underwent clinical examinations and swept-source optical coherence tomography scans (PlexElite-9000 device) centered on the fovea. Scans with quality scores >6 were included. Eyes with any signs of neovascular AMD or geographic atrophy were excluded. The choroidal layer was segmented using ResUNet model and volumetric smoothing. Phansalkar thresholding was used to binarize the choroidal vasculature. The three-dimensional maps were divided into five sectors. The three largest vessels in each sector were measured to determine the mean choroidal vessel diameter (MChVD) and inter-vessel distance (IVD). Volumetric choroidal thickness (ChT) and vascularity index (CVI) were also calculated.</p><p><strong>Results: </strong>This retrospective cross-sectional study analyzed 60 eyes from 45 dAMD patients (27 early-stage, 33 intermediate-stage) and 26 eyes from 16 healthy controls. The average MChVD was increased in dAMD eyes compared to healthy eyes (239.559 ± 47.058 µm vs. 197.873 ± 49.047 µm, P < 0.001). The average MChVD in each sector increased significantly in eyes with dAMD (P < 0.05). The average IVD was increased significantly in dAMD eyes compared to healthy eyes (234.128 ± 69.537 µm vs. 179.914 ± 49.995 µm, P < 0.001). The average IVD in each sector was significantly increased in eyes with dAMD (P < 0.05). Average ChT and CVI in dAMD were reduced compared to healthy eyes (P < 0.05).</p><p><strong>Conclusions: </strong>Eyes with dAMD demonstrated increased MChVD and IVD and decreased ChT and CVI, possibly related to smaller-vessel atrophy and larger-vessel dilation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"39"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668082","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":"Cysteine Leukotriene Receptor Antagonist-Montelukast Effects on Diabetic Retinal Microvascular Endothelial Cells Curtail Autophagy.","authors":"Ahmed M Awad, Amritha T M Seetharaman, Mohammad Shahadat Hossain, Sally L Elshaer, Rania R Abdelaziz, Manar A Nader, Rajashekhar Gangaraju","doi":"10.1167/iovs.65.13.15","DOIUrl":"10.1167/iovs.65.13.15","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic macular edema (DME) is the primary cause of vision impairment in diabetic retinopathy (DR) patients. A previous study has shown the efficacy of montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, in a diabetic mouse model. This study aims to understand the CysLTR1 signaling in retinal endothelial cells and the impact of montelukast.</p><p><strong>Methods: </strong>Primary human retinal microvascular endothelial cells (HRECs) challenged with 20 ng/mL TNF-α and 30 mM D-glucose (D-glu) for six to 24 hours served as a model of endothelial activation. HRECs were incubated with L-glucose (L-glu) as an osmotic control. CysLTR1 knockdown and montelukast pretreatment assessed CysLTR1 antagonism. Gene expression, protein expression, and cell-permeable dyes were utilized to measure autophagy and inflammation. Transendothelial electrical resistance (TER) and transendothelial migration of mononuclear leukocytes across HRECs monolayer were measured as a functional assessment of vascular permeability.</p><p><strong>Results: </strong>Endothelial activation induced by hyperglycemia and inflammation increased CysLTR1 expression, triggering autophagy within two to six hours, IL-1β production, loss of junction integrity, decreased TER, and increased leukocyte migration within six to 24 hours. Pretreatment with montelukast effectively alleviated these effects, demonstrating its dependence on CysLTR1.</p><p><strong>Conclusions: </strong>Dysfunctional retinal endothelium initiates a self-reinforcing loop of inflammation, autophagy, and compromised integrity associated with heightened CysLTR1 levels. The antagonistic effect of montelukast against CysLTR1 effectively mitigates these detrimental changes. This study reveals CysLTR1 as a potential therapeutic target in treating DME and offers a novel strategy to mitigate detrimental changes in DR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 13","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582962","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}