Investigative ophthalmology & visual science最新文献

{"title":"Longitudinal Study of Changes in Retinal Curvature and its Relationship With Myopia Shift in Chinese Children.","authors":"Yue Wu, Xin Liu, Wenzhe Qian, Yinghai Yu, Siyuan Wu, Bingbing Ni, Bilian Ke","doi":"10.1167/iovs.66.9.37","DOIUrl":"10.1167/iovs.66.9.37","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate longitudinal changes in retinal curvature (RC) among Chinese children and its relationship with myopia progression.</p><p><strong>Methods: </strong>This 12-month longitudinal study included children aged 6 to 16 years, divided into groups based on changes in spherical equivalent refraction (SER) over 1 year: the myopic shift group and the non-myopic shift group. Comprehensive examinations including swept-source optical coherence tomography were performed in each visit. RC was assessed using a customized 3D reconstruction algorithm. The central, temporal, nasal, superior, and inferior quadrates were further divided into nine regions and calculated the average curvature for each. The retinal surface asymmetry index (R-SAI) was calculated to describe regional differences in RC. Statistical analyses were performed to explore correlations between RC changes and myopia progression.</p><p><strong>Results: </strong>Significant increases in central RC were observed in the myopic shift group, particularly in the 0 to 6 mm-diameter central retinal region. Regional analysis showed that significant changes in curvature were observed in the myopic shift group particularly in the 0 to 3 mm central circle (C0), temporal quadrate of 3 to 6 mm (T1), and 6 to 9 mm ring (T2) and inferior quadrate of 3 to 6 mm ring (I1), with the most predominant increase in the T1 region. Negative correlation was found between baseline nasal-temporal R-SAI and myopic shift after controlling confounders. Age, axial length (AL) elongation, and smaller baseline curvature were associated with larger RC changes in the central macular region.</p><p><strong>Conclusions: </strong>RC changes are closely linked to myopia shift. Longitudinal monitoring of RC can serve as a quantitative measure for assessing morphological changes associated with myopia shift in children.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"37"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626306","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":"Natural Course and Risk Factors of Glaucoma Development in the Untreated Fellow Eye in Unilateral Normal-Tension Glaucoma.","authors":"Eun Jung Lee, Do Young Park, Changwon Kee, Jong Chul Han","doi":"10.1167/iovs.66.9.16","DOIUrl":"10.1167/iovs.66.9.16","url":null,"abstract":"<p><strong>Purpose: </strong>To test whether the level of intraocular pressure (IOP) significantly affects the development of glaucoma in the untreated fellow eye of patients with unilateral normal-tension glaucoma (NTG).</p><p><strong>Methods: </strong>Long-term observational study on consecutive patients newly diagnosed with unilateral NTG and followed up for >5 years with more than five IOP measurements. We investigated the factors associated with NTG development in the untreated fellow eye, including the longitudinal IOP profile.</p><p><strong>Results: </strong>A total of 194 patients with a baseline age of 50.5 ± 12.1 years were followed up for 8.4 ± 1.6 years. NTG development in the untreated fellow eye occurred in 48 patients (24.7%), with a mean interval of 5.2 ± 2.1 years. Patients with fellow eye NTG development had significantly higher baseline untreated IOP in both eyes and higher follow-up IOPs in the fellow eye compared to those who did not (all P < 0.05). Kaplan-Meier survival analysis and multivariate Cox regression analysis revealed that an average follow-up IOP ≥14 mm Hg in the fellow eye was associated with a significantly increased risk of glaucoma development compared to those with IOP <14 mm Hg (hazard ratio, 3.626; 95% confidence interval, 1.519-8.654; P = 0.004), particularly for the eyes with baseline IOP ≥14 mm Hg.</p><p><strong>Conclusions: </strong>In this 8-year cohort, we observed NTG development in the untreated fellow eyes in 24.7% of the patients with unilateral NTG. The untreated average follow-up IOP was significantly associated with NTG development, with an average IOP ≥14 mm Hg exhibiting a threefold increased risk.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575498","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":"Evidence for M2 Muscarinic Receptor Antagonist Delay of Myopia Development Through Activation of Kir3.4 Channel in the Retina of Guinea Pigs.","authors":"Hong Zhou, Guimei Zhou, Qin Yang, Jiahao Niu, Runzhe Wang, Huilan Liu, Suwen Hou, Hongsheng Bi, Xuan Liao","doi":"10.1167/iovs.66.9.5","DOIUrl":"10.1167/iovs.66.9.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the association between muscarinic receptor M2 and potassium channel Kir3.4 encoded by gene KCNJ5, as well as their role in guinea pigs with form deprivation myopia (FDM).</p><p><strong>Methods: </strong>One hundred sixty-five 3-week-old guinea pigs were randomly assigned to the following groups: normal control (NC), self-control (SC), form deprivation (FD), lentiviral vector (FD + Vector), KCNJ5 overexpression lentivirus (FD + KCNJ5-OE), vehicle control (FD + DMSO), M2 receptor antagonist (FD + AF-DX 116), and M2 receptor agonist (FD + LY2119620). The association between M2 receptors and retinal potassium channels and effects of retinal K+ concentration on myopia development were investigated by constructing a lentiviral KCNJ5 overexpression and M2 receptor intervention model. Immunohistochemistry and molecular assays were conducted to measure the distribution and expression of Kir3.4-related mRNA and protein in the retina. TUNEL was used to observe the drug toxicity response on the retina.</p><p><strong>Results: </strong>The FD group had higher myopic degree (all P < 0.001) and lower expression levels of Kir3.4 than the NC group (P = 0.008). The FD + KCNJ5-OE group exhibited upregulated Kir3.4 protein expression (P < 0.001), but a significant decrease in myopia degree and K+ concentration (all P < 0.001) compared with the FD + Vector group. The FD + AF-DX 116 group exhibited lower myopic degree, K+ concentration (all P < 0.05), and higher Kir3.4 protein expression (P < 0.001), as well as the FD + LY2119620 group exhibited significantly upregulated myopia degree and K+ concentration (all P < 0.001) compared with the FD + DMSO group.</p><p><strong>Conclusions: </strong>This study is the first to explore the muscarinic receptor-potassium channel connection and its implications in the development of myopia. The M2 receptor may be involved in the development of myopia by regulating retinal Kir3.4 channel and K+ homeostasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540230","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":"In Vivo Characterization of Bruch's Membrane Breaks in Neovascular Age-Related Macular Degeneration Using High-Resolution Optical Coherence Tomography.","authors":"Mai Alhelaly, Ceren Soylu, Giulia Corradetti, Federico Corvi, Alireza Mahmoudi, Rouzbeh Abbasgholizadeh, Giovanni Bellisario, Ye He, Alberto Quarta, Muneeswar G Nittala, Giovanni Staurenghi, SriniVas R Sadda","doi":"10.1167/iovs.66.9.19","DOIUrl":"10.1167/iovs.66.9.19","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the frequency and characteristics of Bruch's membrane (BM) breaks, and their relationship with clinically relevant outcomes in neovascular age-related macular degeneration (nAMD).</p><p><strong>Methods: </strong>Forty-seven eyes (39 patients) with nAMD and type 1 macular neovascularization (MNV) were imaged using high-resolution optical coherence tomography (High-Res OCT; Heidelberg). Foveal-centered 20 degrees × 20 degrees volume scans (1024 × 97, automated real time [ART] = 5-25) were obtained. BM breaks, defined as definite interruptions in the hyper-reflective BM band, were identified within the MNV region. The maximum break extent was measured. Break density, distribution, and eccentricity were also evaluated. BM break parameters were correlated with visual acuity and number of intravitreal injections.</p><p><strong>Results: </strong>Thirty eyes were included for quantitative analysis. Multiple breaks were observed in 76.7% of eyes, with a mean of 4.30 ± 4.15 breaks/eye. Notably, breaks showed a preferential eccentric distribution, tending to be closer to the lesion border (mean eccentricity ratio = 4.33 ± 3.61). Our model suggested that a higher break count was significantly associated with higher injection number (P = 0.042), whereas a greater break length was associated with fewer injections (P = 0.001). There was a trend for a higher break count to be associated with better BCVA, but this was not statistically significant (P = 0.099).</p><p><strong>Conclusions: </strong>Most MNV lesions demonstrated multiple breaks with a tendency for breaks to be in the lesion periphery. The identification of BM breaks appeared to be of clinical relevance as the number and length of the breaks were associated with the number of intravitreal injections. Larger prospective studies are warranted to confirm these findings.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"19"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12248956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583879","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":"Gaze-Induced Optic Nerve Head Deformations Are Greater in High Myopia and Strains Increase With Axial Length.","authors":"Tingting Liu, Ya Xing Wang, Jost B Jonas, Quan V Hoang, Michaël J A Girard, Xiaofei Wang","doi":"10.1167/iovs.66.9.21","DOIUrl":"10.1167/iovs.66.9.21","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate optic nerve head (ONH) deformations caused by horizontal eye movements in high myopia (HM) using in vivo optical coherence tomography (OCT) imaging and finite-element (FE) modeling, and to identify factors influencing these deformations.</p><p><strong>Methods: </strong>A total of 28 HM eyes and 28 non-HM eyes were imaged at baseline, 20° adduction, and 20° abduction positions using OCT. Lamina cribrosa (LC) effective strains were quantified using a three-dimensional tracking algorithm. A baseline FE model of an emmetropic eye with an axial length of 23.5 mm and normal tissues structures and a HM model with elongated axial length and thinner sclera were developed. The effects of varying scleral stiffness and the eye movement center on gaze-induced ONH deformations were explored.</p><p><strong>Results: </strong>In vivo measurement showed that LC strains were significantly greater in HM eyes than in non-HM eyes during adduction (5.95% ± 3.52% vs. 3.65% ± 1.85%; P = 0.002) and abduction (3.35% ± 1.94% vs. 2.29% ± 1.65%; P = 0.016). Strains correlated positively with axial length. FE modeling demonstrated greater gaze-induced LC strains in the HM model compared to the emmetropic model, in both adduction and abduction. A softer sclera reduced LC strains in the HM model, whereas a forward shift in the eye movement center (relative to the geometric center, as seen in HM eyes) increased strain.</p><p><strong>Conclusions: </strong>This study demonstrates that gaze-induced ONH deformations increase with axial elongation. The findings highlight the role of scleral stiffness and eye movement center position in modulating ONH biomechanics, contributing to the understanding of glaucomatous, glaucoma-like, and non-glaucomatous optic neuropathy in HM.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"21"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12249009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583878","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":"Exosomal miRNA Profiling in Liquid Biopsy of Vitreous in Proliferative Diabetic Retinopathy.","authors":"Bin Yan, Jianing Qiu, Yan Yang, Jing Luo, Dan Liu, Lusi Zhang, Zhishang Meng, Huiling Li, Xiaojian Guo, Jun Zeng, Chun Ding, Manyun Xie, Kejun Long","doi":"10.1167/iovs.66.9.24","DOIUrl":"10.1167/iovs.66.9.24","url":null,"abstract":"<p><strong>Purpose: </strong>Proliferative diabetic retinopathy (PDR) is a severe microvascular complication of diabetes mellitus. Although exosomes participate in various pathologic processes, their role in ocular pathologies is unclear. This study profiled exosomal microRNAs (exo-miRNAs) in the vitreous humor (VH) of patients with PDR to elucidate their regulatory roles in PDR pathogenesis.</p><p><strong>Methods: </strong>VH samples were obtained from 23 patients with PDR and 17 non-diabetic controls. Exosomes were isolated using ultracentrifugation and characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blot. High-throughput sequencing identified differentially expressed miRNAs (DEMs), followed by target gene prediction and bioinformatic analyses. The top DEMs were validated using quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Exosomes were isolated and characterized from VH samples. Sequencing analysis identified 843 unique miRNAs, with 60 showing significant differential expression between PDR and control groups (28 upregulated and 32 downregulated). The miR-451a and miR-486-5p were most upregulated; miR-204-5p and miR-211-5p were most downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed DEM target genes enriched in endocrine, metabolic, signaling transduction, and intercellular adhesion pathways, notably cGMP-PKG, mTOR, and cAMP pathways. Network analysis identified miR-486-5p and miR-451a as key hubs. Validation by qRT-PCR confirmed the differential expression in the sequencing analysis.</p><p><strong>Conclusions: </strong>This study provides the comprehensive profile of vitreous exo-miRNAs in patients with PDR, identifying key DEMs and their potential regulatory networks. These findings indicate that vitreous exo-miRNAs, specifically miR-204-5p and miR-486-5p, represent promising diagnostic biomarkers and potential therapeutic targets for PDR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600434","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":"Growth Curve for Infant's \"Fixation To Light\" Using Gaze Reaction Time.","authors":"Monika Thakur, Ranindita Saha, Krishnaveni Nagarajan, Murali Murugavel, Himabindu Singh, PremNandhini Satgunam","doi":"10.1167/iovs.66.9.26","DOIUrl":"10.1167/iovs.66.9.26","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the developmental pattern of infant's gaze initiation time (reaction time) as a function of age. To fit a growth curve model to this function, we hypothesized that reaction time would reduce with age.</p><p><strong>Methods: </strong>A cross-sectional study was conducted. Six hundred ninety-four (694) healthy infants (age = 3-8 months) participated. Infant's gaze reaction time to light stimuli was measured using Baby Vision Screener (BaViS). The BaViS is a dome-shaped device that presents LED stimuli. Infants were tested while in a supine position under this dome in a dark room. The examiner presented the LED stimuli and monitored and recorded the infant's gaze response using a real-time video feed. reaction time was obtained through semi-automated video processing. reaction time was modeled as a function of age using the Box-Cox power exponential generalized additive model for location, scale, and shape (GAMLSS) to generate a growth curve.</p><p><strong>Results: </strong>Reaction time was quantifiable in 682 infants. reaction time significantly (P < 0.001) reduced with age (e.g. 3-month-old infants had a median reaction time of 684 ms [P25 and P75 = 548 and 846 ms] whereas 8-month-old infants had 397 ms [350 ms and 457 ms] in the upper visual field). The reaction time distribution in the growth curve was wider for younger infants than for older infants (e.g. the reaction time range between the 5th and the 95th percentile was 925 ms for 3-month-old and 385 ms for 8-month-old infants).</p><p><strong>Conclusions: </strong>As hypothesized, a developmental trend for gaze response was observed. The reduction in variability of this behavioral measure with age could be indicative of neural maturation. The percentile growth curve of reaction time obtained from this behavioral study can be explored further as a quantitative clinical measure for evaluating infant vision.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"26"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255174/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600436","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":"Expression of Concern for: Assessment of Neuroprotective Effects of Glutamate Modulation on Glaucoma-Related Retinal Ganglion Cell Apoptosis In Vivo.","authors":"","doi":"10.1167/iovs.66.9.34","DOIUrl":"10.1167/iovs.66.9.34","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12266293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608432","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":"Investigation of ABCA4 Missense Variants and Potential Small Molecule Rescue in Retinal Organoids.","authors":"Davide Piccolo, Paul Sladen, Rosellina Guarascio, Kalliopi Ziaka, Michael E Cheetham","doi":"10.1167/iovs.66.9.58","DOIUrl":"10.1167/iovs.66.9.58","url":null,"abstract":"<p><strong>Purpose: </strong>ABCA4-related retinopathy is the most common monogenic eye disorder in the world and is currently untreatable. Missense variants in ABCA4 constitute ∼60% of causal ABCA4-related retinopathy variants, often resulting in misfolded or dysfunctional protein products. Despite their prevalence, the molecular mechanisms by which these missense mutations impair ABCA4 function are not fully understood, primarily due to limitations in suitable cellular models. In this study, we investigated the cellular and molecular consequences of ABCA4 missense variants using a human photoreceptor-like model system.</p><p><strong>Methods: </strong>We used CRISPR/Cas9 technology to introduce two ABCA4 missense misfolding variants, T983A and R2077W, which are associated with ABCA4-associated retinopathy, into control induced pluripotent stem cells (iPSCs). The iPSCs were differentiated into retinal organoids, characterized and treated with small molecules.</p><p><strong>Results: </strong>The expression level of ABCA4 missense proteins was reduced compared to WT ABCA4 suggesting the variants were degraded in a photoreceptor-like environment. The localization of the missense variants was also altered with negligible ABCA4 detectable in the retinal organoid outer segments compared to the isogenic control. Two small molecule compounds, AICAR and 4-PBA, previously identified as potential ABCA4 folding correctors in vitro, were tested for their ability to enhance ABCA4 traffic to the outer segment. The compounds did not appear to promote ABCA4 folding and traffic in photoreceptors and instead led to a decrease in ABCA4 transcript levels and protein.</p><p><strong>Conclusions: </strong>These data highlight that retinal organoids are an exquisite model to investigate pathogenic variants in ABCA4 and test small compounds for translation to the human retina.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"58"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690303","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":"TRPV1 Defends the Healthy Murine Cornea Against Staphylococcus aureus Adhesion Independently of Sensory Nerve Firing.","authors":"Orneika Flandrin, Yujia Yang, Sara Abboud, Naren G Kumar, Ananya Datta, Eric Jedel, Diana Bautista, David Evans, Suzanne M J Fleiszig","doi":"10.1167/iovs.66.9.61","DOIUrl":"10.1167/iovs.66.9.61","url":null,"abstract":"<p><strong>Purpose: </strong>Previously, we showed that transient receptor potential ion channels TRPA1 and TRPV1 selectively protect the cornea against bacterial adhesion, with TRPA1 countering the Gram-negative pathogen Pseudomonas aeruginosa (P. aeruginosa) and TRPV1 countering environmental bacteria. Here, we explored parameters of this specificity using a Gram-positive pathogen Staphylococcus aureus (S. aureus).</p><p><strong>Methods: </strong>Healthy corneas of C57BL/6J wild-type (WT), TRPA1 (-/-), or TRPV1 (-/-) mice were challenged with S. aureus for 4 or 6 hours. Some experiments instead/also used resiniferatoxin (RTX) to deplete TRPV1-expressing nerves, JNJ-17203212 to selectively antagonize TRPV1, or the anesthetic bupivacaine to inhibit nerve firing. Adherent bacteria were quantified using fluorescence in situ hybridization (FISH) labeling (16S rRNA-targeted probe). Lyz2+, CD11c+, and CD45+ cells were visualized/quantified using hybrid mT/mG + LysMcre mice (red cell membranes; Lyz2+-GFP), CD11c+-YFP mice, and anti-CD45-antibody, respectively.</p><p><strong>Results: </strong>Corneas of TRPV1 (-/-) not TRPA1 (-/-) mice were found more susceptible to S. aureus adhesion compared to WT. Accordingly, either ablation of TRPV1-expressing nerves or TRPV1 antagonism increased adhesion. Defense against S. aureus adhesion did not depend on nerve firing. Despite having no significant impact on CD11c+ or Lyz2+ cell numbers, the S. aureus challenge increased CD45+ cell counts, also dependent on TRPV1-expressing nerves, and it increased Lyz2+ cell sphericity and volume.</p><p><strong>Conclusions: </strong>Healthy corneas utilize TRPV1 to protect against S. aureus adhesion independently of sensory nerve firing. This contrasts with defense against P. aeruginosa adhesion which requires TRPA1 and nerve firing. How the differential immune cell responses to these two pathogens relate to TRP-dependent defense against adhesion remains to be determined.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 9","pages":"61"},"PeriodicalIF":4.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690305","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}