Investigative ophthalmology & visual science最新文献

{"title":"Eye Movements and the Intraorbital Subarachnoid Space: Potential Contribution of Altered Cerebrospinal Fluid Pumping in Optic Neuropathies.","authors":"Joseph L Demer, Robert A Clark, Soh Youn Suh, JoAnn A Giaconi, Kouros Nouri-Mahdavi, Simon K Law, Laura Bonelli, Anthony C Arnold, Peter Quiros, Anne L Coleman, Joseph Caprioli","doi":"10.1167/iovs.66.1.53","DOIUrl":"10.1167/iovs.66.1.53","url":null,"abstract":"<p><strong>Purpose: </strong>The optic nerve (ON) is mechanically perturbed by eye movements that shift cerebrospinal fluid (CSF) within its surrounding dural sheath. This study compared changes in ON length and CSF volume within the intraorbital ON sheath caused by eye movements in healthy subjects and patients with optic neuropathies.</p><p><strong>Methods: </strong>Twenty-one healthy controls were compared with 11 patients having primary open angle glaucoma (POAG) at normal intraocular pressure (IOP), and 11 with chronic non-arteritic anterior ischemic optic neuropathy (NA-AION). High resolution magnetic resonance imaging (MRI) was performed in central and eccentric gazes, and analyzed to determine ON partial volume and gaze-related changes in ON path redundancy, ON elongation, and intrasheath CSF volume.</p><p><strong>Results: </strong>ON volume was subnormal in both POAG and NA-AION. In all subjects, ON path redundancy decreased similarly from abduction to central gaze to adduction; in healthy subjects, the ON path was also significantly less redundant in infraduction and supraduction. The ON elongated significantly in adduction in controls and NA-AION but not in POAG. In all groups, CSF volume was 40 to 50 mm3 in central gaze, and significantly decreased in adduction, abduction, and supraduction in controls but subnormally in adduction only in POAG and NA-AION. The globe translated laterally more than normal in NA-AION but did not retract.</p><p><strong>Conclusions: </strong>Horizontal gaze and supraduction change subarachnoid CSF volume around the retrobulbar ON. Eye movements might thus pump CSF to promote ON health, but this effect is subnormal in adduction in POAG and NA-AION, suggesting that retrobulbar CSF pumping is associated with chronic forms of these optic neuropathies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"53"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11758931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023399","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":"The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.","authors":"Joseph B Lin, Rajendra S Apte","doi":"10.1167/iovs.66.1.47","DOIUrl":"10.1167/iovs.66.1.47","url":null,"abstract":"<p><p>Ever since the US Food and Drug Administration (FDA) approved the first vascular endothelial growth factor (VEGF) antagonist 2 decades ago, inhibitors of VEGF have revolutionized the treatment of a variety of ocular disorders involving pathologic neovascularization and retinal exudation. In this perspective, we evaluate the current status of anti-VEGF therapies and the real-world challenges encountered with maintaining therapeutic outcomes. Finally, we describe novel VEGF-based and combinatorial approaches that are in clinical development.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"47"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005523","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":"Relationship Between Intraocular Pressure and the True Rate of Functional and Structural Progression in the United Kingdom Glaucoma Treatment Study.","authors":"Giovanni Montesano, Alessandro Rabiolo, Giovanni Ometto, David P Crabb, David F Garway-Heath","doi":"10.1167/iovs.66.1.32","DOIUrl":"10.1167/iovs.66.1.32","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the effect of average intraocular pressure (IOP) on the true rate of glaucoma progression (RoP) in the United Kingdom Glaucoma Treatment Study (UKGTS).</p><p><strong>Methods: </strong>UKGTS participants were randomized to placebo or Latanoprost drops and monitored for up to two years with visual field tests (VF, 24-2 SITA standard), IOP measurements, and optic nerve imaging. We included eyes with at least three structural or functional assessments (VF with <15% false-positive errors). Structural tests measured rim area (RA) with Heidelberg retina tomography (HRT) and average peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT). One eye of 436 patients (222 on Latanoprost) was analyzed. A Bayesian hierarchical model estimated the true RoP of VF and structural metrics, and their correlations, using sign-reversed multivariable exponential distribution. RA and pRNFL measurements were converted to a dB scale, matching the VF metric (mean deviation [MD]). The effect of average IOP on the true RoPs was estimated.</p><p><strong>Results: </strong>True RoP at the mean average IOP (17 mm Hg) was faster (P < 0.001) for VF-MD (-0.59 [-0.73, -0.48] dB/year) than HRT-RA (-0.05 [-0.07, -0.03] dB/year) and OCT-pRNFL (-0.08 [-0.11, -0.06] dB/year). The proportional acceleration of RoP per mm Hg increase was, however, not significantly different (smallest P = 0.15). Accounting for the structural floor-effect largely eliminated the differences in RoPs (smallest P = 0.25).</p><p><strong>Conclusions: </strong>VF appeared to deteriorate at a faster rate than structural measurements. However, this could be explained by the floor-effect from nonfunctional tissue. IOP induced a similar acceleration in RoP per mm Hg increase.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"32"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978466","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":"Proteomics Reveals Mechanisms of Delayed Keratoconus Progression: A Study of Corneas Following Two Light-Activated Crosslinking Treatments.","authors":"Demi H J Vogels, Jurriaan Brekelmans, Ronny Mohren, Naomi R N Vos, Alexander Brandis, Arie L Marcovich, Berta Cillero-Pastor, Avigdor Scherz, Vanessa L S LaPointe, Mor M Dickman","doi":"10.1167/iovs.66.1.64","DOIUrl":"10.1167/iovs.66.1.64","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to elucidate on changes in biological pathways in rabbit corneas induced by two methods of light-activated corneal stiffening: topical application of riboflavin with dextran (RF-D) or WST11 with dextran (WST-D) followed by ultraviolet A (UVA) or near-infrared (NIR) illumination, respectively.</p><p><strong>Methods: </strong>Rabbit corneas were mechanically de-epithelialized, then left untreated (N = 3) or treated with either RF-D/UVA (N = 3) or WST-D/NIR (N = 3). After one week, quantitative proteomics was performed on untreated, RF-D/UVA- and WST-D/NIR-treated corneas. Pathway enrichment analysis was performed to identify the biological processes associated with the treatments. To identify the abundance and spatial distribution of lipids in the untreated, WST-D/NIR- and RF-D/UVA-treated corneal stroma, lipid mass spectrometry imaging was performed together with hematoxylin and eosin staining.</p><p><strong>Results: </strong>Between RF-D/UVA- and WST-D/NIR-treated corneas, 37 and 39 proteins, respectively, were differentially expressed compared to untreated corneas (P < 0.05). Pathway enrichment analysis showed the effect of RF-D/UVA treatment on cell metabolism and terminal differentiation of keratocytes, while WST-D/NIR modified extracellular matrix regulation and the mitogen-activated protein kinase signaling cascade. When comparing the RF-D/UVA and WST-D/NIR treatment, 74 proteins were differentially expressed, affecting cellular metabolism and respiration, complement activation, the activation of matrix metalloproteinases, and lipoprotein metabolism. The lipid profile for the RF-D/UVA- and WST-D/NIR-treated stromas were similar, whereas differences were observed comparing both treatments to untreated corneal stroma.</p><p><strong>Conclusions: </strong>Proteomics indicated a metabolic shift from oxidative phosphorylation to glycolysis and hypoxia after RF-D/UVA treatment. In contrast, WST-D/NIR stiffening maintained normal respiration and involved extracellular matrix remodeling.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"64"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065545","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":"miRNA Expression Profile in Primary Limbal Epithelial Cells of Aniridia Patients.","authors":"Mahsa Nastaranpour, Shweta Suiwal, Tanja Stachon, Fabian N Fries, Maryam Amini, Berthold Seitz, Eckart Meese, Nicole Ludwig, Nóra Szentmáry","doi":"10.1167/iovs.66.1.20","DOIUrl":"10.1167/iovs.66.1.20","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluates the microRNA (miRNA) expression profile in primary limbal epithelial cells (pLECs) of patients with aniridia.</p><p><strong>Methods: </strong>Primary human LECs were sampled and isolated from 10 patients with aniridia and 10 healthy donors. The miRNA profile was analyzed using miRNA microarrays. The biological roles of miRNA-validated target genes were delineated in silico by the enrichment analyses of the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The expression of the most deregulated miRNAs was analyzed using quantitative real-time PCR (qRT-PCR).</p><p><strong>Results: </strong>Microarray analysis revealed 10 differentially expressed miRNAs in pLECs of patients with aniridia relative to healthy controls (fold change = ≤ -2 or ≥ +2), nevertheless these were only differentially expressed using an unadjusted P value < 0.05. The qRT-PCR validation confirmed the significantly altered expression of miR-138-5p in pLECs of patients with aniridia (P = 0.005). In silico GO analysis of miR-138-5p target genes revealed the potential biological functions of miR-138-5p in regulating various cellular and molecular processes, including the positive regulation of cell motility, G1/S phase cell cycle transition, and cell migration, as well as the negative role in regulating epithelial cell differentiation. Pathway analysis highlighted the main involvement of the PI3K-Akt, Hippo, Wnt, Focal adhesion, cAMP, p53, IL-17, Jak-STAT, and MAPK-signaling pathways.</p><p><strong>Conclusions: </strong>This study revealed miRNA expression profile in pLECs of patients with aniridia using miRNA microarray and identified miRNAs that had not been previously reported for aniridia LECs. Our study also provides functional and pathway information that can be used to predict possible mechanism of miRNA function in LECs, thereby bridging the gap in the pathogenesis of AAK studies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948413","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":"Unveiling Statins and Genetics in Age-Related Macular Degeneration Progression: What Is the Appropriate Modeling Strategy?","authors":"Blondy Kayembe Mulumba, Karen Leffondré, Pierre Joly, Marie-Noëlle Delyfer, Cécile Delcourt","doi":"10.1167/iovs.66.1.25","DOIUrl":"10.1167/iovs.66.1.25","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"25"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948887","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":"Simvastatin-Induced Ferroptosis in Orbital Fibroblasts in Graves' Ophthalmopathy.","authors":"Lujue Wang, Yuan Li, Tongxin Niu, Jing Deng, Yuxian Shi, Yating Liu, Boding Tong, Xin Qi, Dan Cao, Yongguang Tao, Yunping Li","doi":"10.1167/iovs.66.1.56","DOIUrl":"10.1167/iovs.66.1.56","url":null,"abstract":"<p><strong>Purpose: </strong>Graves' ophthalmopathy (GO), the most common extrathyroidal manifestation of Graves' disease, is disabling and disfiguring. Recent studies have shown that statins have a protective effect on individuals with GO. Statins were reported to trigger ferroptosis in some disorders, but little is known about whether statins protect against GO via ferroptosis. The aim of this study was to explore whether ferroptosis is involved in the protective effect of simvastatin on GO.</p><p><strong>Methods: </strong>GO-OFs, which are orbital fibroblasts (OFs) derived from individuals with GO, were analyzed for lipogenesis by RT-qPCR and Red Oil O staining posttreatment with simvastatin. CCK-8 assays, flow cytometric analysis, and transmission electron microscopy (TEM) were used to compare the sensitivity of GO-OFs and control-OFs to erastin-induced ferroptosis. The ferroptosis levels in the GO-OFs were evaluated by measuring cell viability, reactive oxygen species (ROS) levels, and lipid peroxidation levels and performing TEM analysis after treatment with simvastatin and Fer-1.</p><p><strong>Results: </strong>The GO-OFs were resistant to erastin-induced ferroptosis. The viability and lipogenesis of the GO-OFs were significantly decreased, while the levels of ROS, lipid peroxidation, and the ferroptosis marker ACLS4 were increased upon treatment with simvastatin.</p><p><strong>Conclusions: </strong>Our study indicated that ferroptosis plays an important role in the pathogenesis of GO and that simvastatin may induce ferroptosis, suggesting that this drug could serve as a novel therapeutic agent for GO.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"56"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032885","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":"Artificial Intelligence in Predicting Ocular Hypertension After Descemet Membrane Endothelial Keratoplasty.","authors":"Min Seok Kim, Heesuk Kim, Hyung Keun Lee, Chan Yun Kim, Wungrak Choi","doi":"10.1167/iovs.66.1.61","DOIUrl":"10.1167/iovs.66.1.61","url":null,"abstract":"<p><strong>Purpose: </strong>Descemet membrane endothelial keratoplasty (DMEK) has emerged as a novel approach in corneal transplantation over the past two decades. This study aims to identify predisposing risk factors for post-DMEK ocular hypertension (OHT) and develop a preoperative predictive model for post-DMEK OHT.</p><p><strong>Methods: </strong>Patients who underwent DMEK at Gangnam Severance Hospital between 2017 and 2024 were included in the study. Four machine learning models-XGBoost, random forest, CatBoost, and logistic regression-were trained to assess feature importance and develop a predictive classifier. An ensemble of these four models was used as the final predictive model. The ensemble model identified clinically significant patients for prediction or exclusion.</p><p><strong>Results: </strong>A total of 106 eyes from patients who underwent DMEK were analyzed, with 31 eyes (29.2%) experiencing post-DMEK OHT. The final ensemble model achieved clinically significant classification for 61 eyes (57.5%) in the total patient population. Significant risk factors identified in all four models included angle recess area (ARA), best-corrected visual acuity, donor graft size, angle-to-angle distance, crystalline lens rise, and central corneal thickness. The average accuracy, precision, recall, area under the receiver operating characteristic curve, and area under the precision-recall curve values of the ensemble model obtained by a 5-fold cross-validation were 80.2%, 60.0%, 59.7%, 82.3%, and 68.0%, respectively.</p><p><strong>Conclusions: </strong>This study identified significant risk factors for post-DMEK OHT and highlighted the importance of ocular topographic measures in risk assessment. The development of a final machine learning model to differentiate between clinically predictable patient groups demonstrates the clinical utility of the proposed model for predicting post-DMEK OHT.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"61"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046549","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":"Horizontal Gaze Tolerance and Its Effects on Visual Sensitivity in Glaucoma.","authors":"Takashi Nishida, Takuhei Shoji, Robert N Weinreb, Saori Yamaguchi, Izumi Mine, Akane Kosaka, Kei Shinoda","doi":"10.1167/iovs.66.1.59","DOIUrl":"10.1167/iovs.66.1.59","url":null,"abstract":"<p><strong>Purpose: </strong>This study evaluates the effect of 6° horizontal gaze tolerance on visual field mean sensitivity (MS) in patients with glaucoma using a binocular head-mounted automated perimeter, following findings of structural changes in the posterior globe from magnetic resonance imaging and optical coherence tomography.</p><p><strong>Methods: </strong>In this cross-sectional study, a total of 161 eyes (85 primary open-angle glaucoma [POAG] and 76 healthy) from 117 participants were included. Logistic regression and 1:1 matched analysis assessed the propensity score for glaucoma and healthy eyes, considering age, sex, and axial length as confounders. Visual field tests were performed with the imo perimeter (CREWT Medical Systems, Inc., Tokyo, Japan) at central gaze, 6° abduction, and 6° adduction positions as fixation points. A mixed-effects model was used to compare MS under all conditions.</p><p><strong>Results: </strong>The analysis included a total of 82 eyes, with 41 POAG and 41 healthy after matching. The mean (standard deviation) age was 68.0 (11.0) years, with a mean deviation of -9.9 (6.6) dB for POAG and -1.0 (1.9) dB for healthy eyes using Humphrey field analysis 24-2. MS did not significantly differ among central gaze (27.0 [1.8] dB), abduction (27.1 [1.9] dB), and adduction (26.9 [2.2] dB) in healthy eyes (P = 0.650). However, MS was significantly lower for adduction (17.2 [5.9] dB) compared to central gaze (18.1 [5.9] dB) and abduction (17.9 [5.9] dB) in glaucoma eyes (P = 0.001 and P = 0.022, respectively).</p><p><strong>Conclusions: </strong>Horizontal gaze, especially in adduction, significantly reduces visual sensitivity in glaucoma, suggesting a specific vulnerability associated with eye movement. This finding highlights the importance of eye positioning in glaucoma, warranting further investigation of its clinical significance.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"59"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046606","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":"Novel Anti-Microbial/Anti-Inflammatory Combination Improves Clinical Outcome of Bacillus cereus Endophthalmitis.","authors":"Md Huzzatul Mursalin, Phillip S Coburn, Luis Longoria-Gonzalez, Roger Astley, Vincent A Fischetti, Michelle C Callegan","doi":"10.1167/iovs.66.1.39","DOIUrl":"10.1167/iovs.66.1.39","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to explore the therapeutic potential of the novel combination of Bacillus bacteriophage lysin (PlyB) and a synthetic TLR2/4 inhibitor (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, OxPAPC) in the treatment of experimental Bacillus cereus endophthalmitis.</p><p><strong>Methods: </strong>C57BL/6J mice were injected with 100 colony forming units (CFUs) Bacillus cereus to induce endophthalmitis. Two hours postinfection, groups of mice were treated with either PlyB, PlyB with OxPAPC, or the groups were left untreated to serve as a control. A group of uninfected mice was injected with only PlyB to serve as a treatment control. Eight hours post-treatment, infected/treated mice were analyzed for bacterial counts, retinal function, histology, and inflammation.</p><p><strong>Results: </strong>Groups treated with PlyB alone or PlyB/OxPAPC showed significantly reduced bacterial loads compared with untreated eyes. Compared with untreated eyes, PlyB and PlyB/OxPAPC-treated eyes retained significant A-wave and B-wave function. PlyB/OxPAPC-treated eyes retained greater A- and B-wave function compared with eyes treated with PlyB alone. Histology showed that retinal structures were well preserved, and retinal layers were distinguishable in eyes treated with PlyB and PlyB/OxPAPC. Ninety-five percent of infiltrating CD45+ cells in infected untreated eyes were Ly6G+/Ly6C+ neutrophils. Infected eyes treated with PlyB and PlyB/OxPAPC had significantly reduced numbers of CD45+ immune cells compared with untreated eyes. Eyes treated with PlyB/OxPAPC had a significantly lower number of neutrophils than eyes treated with PlyB alone.</p><p><strong>Conclusions: </strong>These results demonstrated that the novel combination of bacteriophage lysin and TLR2/4 inhibitor was a successful treatment option for treating experimental Bacillus cereus endophthalmitis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 1","pages":"39"},"PeriodicalIF":5.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983588","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}