Investigative ophthalmology & visual science最新文献

{"title":"Roflumilast Attenuates Microglial Senescence and Retinal Inflammatory Neurodegeneration Post Retinal Ischemia Reperfusion Injury Through Inhibiting NLRP3 Inflammasome.","authors":"Chunlian Ou, Yiwei Lin, Jing Wen, Hongyang Zhang, Ying Xu, Naiyuan Zhang, Qiong Liu, Yingzi Wu, Jing Xu, Jing Wu","doi":"10.1167/iovs.65.12.38","DOIUrl":"https://doi.org/10.1167/iovs.65.12.38","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ischemia-reperfusion (RIR) injury is implicated in various retinal diseases, leading to retinal ganglion cells (RGCs) degeneration. Microglial senescence exacerbates inflammation, contributing to neurodegeneration. This study aimed to investigate the potential therapeutic role of Roflumilast (Roflu) in ameliorating microglial senescence and neuroinflammation following RIR injury.</p><p><strong>Methods: </strong>C57BL/6J mice underwent RIR surgery, and Roflu treatment was administered intraperitoneally. BV2 microglial cells were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) to simulate ischemic conditions in vitro. SA-β-gal staining was used to detect cellular senescence. Quantitative PCR and ELISA were used to examine the levels of senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin (H&E) staining was performed on retinal sections to assess retinal morphology and thickness. Surviving RGCs were labeled and quantified in retinal whole-mounts using immunofluorescence (IF). Furthermore, Western blot and IF staining were used to quantify the proteins associated with the cell cycle and NLRP3 inflammasomes.</p><p><strong>Results: </strong>Roflu treatment reduced microglial senescence, ROS production, and secretion of pro-inflammatory cytokines in OGD/R-exposed BV2 cells. It also restored cell proliferation capacity and reversed OGD/R-induced cell cycle arrest. In vivo, Roflu alleviated retinal senescence, preserved retinal thickness, and protected against RGCs death in the RIR mouse model. Mechanistically, Roflu inhibited the NLRP3 inflammasome activation and suppressed DNA damage signaling pathway in microglia.</p><p><strong>Conclusions: </strong>Roflu exerts neuroprotective effects by mitigating microglial senescence and inflammation via inhibition of the NLRP3 inflammasome in RIR injury. These findings suggest that Roflu may serve as a promising therapeutic strategy for retinal diseases associated with ischemic injury by targeting microglial senescence.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"38"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500610","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":"Mesenchymal Stem Cells-Derived Exosomal miR-223-3p Alleviates Ocular Surface Damage and Inflammation by Downregulating Fbxw7 in Dry Eye Models.","authors":"Guifang Wang, Yujie Zhu, Yuzhen Liu, Mulin Yang, Li Zeng","doi":"10.1167/iovs.65.12.1","DOIUrl":"10.1167/iovs.65.12.1","url":null,"abstract":"<p><strong>Purpose: </strong>Our previous study indicated that exosomes derived from mouse adipose-derived mesenchymal stem cells (mADSC-Exos) alleviated the benzalkonium chloride (BAC)-induced mouse dry eye model. However, the specific active molecules in mADSC-Exos that contribute to anti-dry eye therapy remain unidentified. In this study, we aimed to investigate the efficacy and mechanisms of miR-223-3p derived from mADSC-Exos in dry eye models.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to determine miR-223-3p derived from mADSC-Exos that exerted anti-inflammatory effects on hyperosmolarity-induced mouse corneal epithelial cells (MCECs). The therapeutic efficacy of miR-223-3p was evaluated in mice with dry eye induced by either BAC or scopolamine (Scop). Mice were randomly assigned to 5 groups: sham, model, miR-223-3p overexpression, miR-223-3p knockdown, and 0.1% pranoprofen (positive group). Post-treatment, the severity of dry eye symptoms, and the pro-inflammatory cytokine levels were assessed. The effect of miR-223-3p on silencing the target gene was verified using ELISA and dual luciferase reporter assays.</p><p><strong>Results: </strong>The mADSC-Exos that knocked out miR-223-3p did not reduce interleukin (IL)-6 content. Supplementing with miR-223-3p could restore the reduction of IL-6. The miR-223-3p effectively ameliorated ocular surface damage and decreased pro-inflammatory cytokines or chemokines in both BAC- and Scop-induced mouse dry eye models. Furthermore, miR-223-3p inhibited cell apoptosis. F-box and WD repeat domain-containing 7 (Fbxw7) was the potential direct target of miR-223-3p. The miR-223-3p suppressed the 3'-untranslated region of Fbxw7. The Fbxw7 knockdown suppressed hyperosmolarity-induced inflammation in MCECs.</p><p><strong>Conclusions: </strong>The mADSC-derived exosomal miR-223-3p mitigates ocular surface damage and inflammation, indicating its potential as a promising treatment option for dry eye.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346863","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":"Fetuin-B Interacts With Insulin Receptor-β and Promotes Insulin Resistance in Retina Cells.","authors":"Wenyi Zhang, Xin Wang, Shuwei Tian, Jianming Wang, Aiyi Zhou","doi":"10.1167/iovs.65.12.16","DOIUrl":"10.1167/iovs.65.12.16","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the correlation between insulin and Fetuin-B (FETUB) and the influence of FETUB on insulin signaling pathway in diabetic retinopathy (DR).</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assay (ELISA) was used to analyze FETUB and insulin levels in the serum and aqueous fluid of patients with DR and healthy controls. Quantitative PCR (q-PCR), Western blotting, and ELISA were used to examine FETUB expression in ARPE-19, BV2, and Müller cells under insulin stimulation. Co-immunoprecipitation was used to investigate the interaction of FETUB with insulin receptor-β (IRβ). Insulin resistance (IR)-BV2 and IR-Müller cells were treated with FETUB recombinant protein or FETUB short hairpin RNA (shRNA) to explore the influence of FETUB on insulin signaling pathway in DR. LY294002 (a PI3K pathway inhibitor) was used to determine whether FETUB affects glucose metabolism via the PI3K/Akt pathway.</p><p><strong>Results: </strong>In aqueous fluid, FETUB concentrations were positively correlated with insulin levels. FETUB expression increased in Müller and BV2 cells under insulin regulation, and FETUB interacted with IRβ in retinal cells and mice retina. The interaction between IRβ and FETUB increased in BV2 and Müller cells under high-glucose than in controls. Insulin signaling pathway activation was suppressed in FETUB recombinant protein-treated BV2 and Müller cells but increased in FETUB shRNA-transfected cells. FETUB shRNA could not reverse LY294002-mediated inhibition of glucose transporter-4 expression.</p><p><strong>Conclusions: </strong>Retinal cells are the source of insulin-regulated FETUB. The FETUB interacts with IRβ and affects insulin signaling pathway in BV2 and Müller cells. FETUB may aggravate IR in BV2 and Müller cells via the PI3K/Akt pathway.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390591","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":"Rapid Amplification of Cerebrospinal Fluid Pressure as a Possible Mechanism for Optic Nerve Sheath Bleeding in Infants With Nonaccidental Head Injury.","authors":"Peter S Stewart, Bindi S Brook, Oliver E Jensen, Tamsin A Spelman, Robert J Whittaker, Moussa A Zouache","doi":"10.1167/iovs.65.12.9","DOIUrl":"10.1167/iovs.65.12.9","url":null,"abstract":"<p><strong>Purpose: </strong>Subdural hemorrhage along the optic nerve (ON) is a histopathological indicator of abusive head trauma (AHT) in infants. We sought to determine if this bleeding could be caused by an abrupt increase in intracranial pressure transmitted to cerebrospinal fluid (CSF) at the optic foramen (OF).</p><p><strong>Methods: </strong>A theoretical model is developed to simulate the effect of a pressure perturbation of maximal amplitude P applied at the optic foramen for a short duration T on the CSF-filled ON subarachnoid space (ONSAS). The ONSAS is modelled as a fluid-filled channel with an elastic wall representing the flexible ONSAS-arachnoid/dura interface. A constitutive law describing the relationship between CSF pressure and ONSAS deformation is inferred from published measurements. CSF pressure profiles along the ONSAS are examined systematically over a broad range of P and T.</p><p><strong>Results: </strong>The pressure perturbation initiated at the OF produces a pressure wave that stretches the ONSAS. This wave propagates rapidly along the ONSAS toward the scleral end of the ON, where it is reflected back toward the brain. For sufficiently small T a shock wave with amplification up to six times larger than P over a timescale of tens of milliseconds is observed at the scleral end of the ON. Comparatively smaller amplifications are observed for slower perturbations.</p><p><strong>Conclusions: </strong>A sudden increase in CSF pressure in the cranial cavity can cause a rapid expansion of the ONSAS, which may lead to rupture of the bridging blood vessels. Our study predicts a plausible mechanism for subdural hemorrhage that occurs in abusive head trauma in infants.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380769","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":"Trabecular Meshwork Abnormalities in a Model of Congenital Glaucoma Due to LTBP2 Mutation.","authors":"Odalys Torné, Kazuya Oikawa, Leandro B C Teixeira, Julie A Kiland, Gillian J McLellan","doi":"10.1167/iovs.65.12.28","DOIUrl":"10.1167/iovs.65.12.28","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize early trabecular meshwork (TM) morphologic abnormalities in a feline model of human primary congenital glaucoma (PCG) caused by mutation in LTBP2.</p><p><strong>Methods: </strong>Eyes from 41 cats, including 19 normal and 22 homozygous for LTBP2 mutation, across various postnatal stages (birth, 2 weeks, 5 weeks, and 12 weeks) were paraformaldehyde fixed, anterior segments dissected, post-fixed in glutaraldehyde, osmicated, and processed and sectioned for transmission electron microscopy. Cell morphology, nuclear shape, and intertrabecular space (ITS) were quantitatively assessed, and the structure of the fibrillar extracellular matrix in the TM was systematically evaluated.</p><p><strong>Results: </strong>The earliest differences in TM morphology between PCG and normal cats were identified at 2 weeks postnatally. Elastic fibers in the TM were discontinuous and disorganized (P = 0.0122), and by 5 weeks of age PCG cats presented significantly less ITS (P = 0.0076) and morphologically rounder TM cells than normal cats (P = 0.0293). By 12 weeks of age, the ITS was further collapsed (P < 0.0001), and the TM cells were morphologically elongated and attenuated in PCG compared to controls (P = 0.0028).</p><p><strong>Conclusions: </strong>In this feline model of PCG due to LTBP2 mutation, development of ultrastructural TM extracellular matrix abnormalities are first observed by 2 weeks and cellular abnormalities by 5 weeks of age. By 12 weeks of age, when intraocular pressure becomes significantly elevated, the TM morphologic abnormalities are already well established. These findings suggest that the postnatal period between 0 and 5 weeks of age is critical for TM and PCG development and progression in cats.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465671","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":"Lifelong Changes in the Choroidal Thickness, Refractive Status, and Ocular Dimensions in C57BL/6J Mouse.","authors":"Tao Tang, Chi Ren, Yi Cai, Yan Li, Kai Wang, Mingwei Zhao","doi":"10.1167/iovs.65.12.26","DOIUrl":"10.1167/iovs.65.12.26","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the changes in choroidal thickness (ChT), refractive status, and ocular dimensions in the mouse eye in vivo using updated techniques and instrumentation.</p><p><strong>Methods: </strong>High-resolution swept-source optical coherence tomography (SS-OCT), eccentric infrared photoretinoscopy, and custom real-time optical coherence tomography were used to analyze choroidal changes, refractive changes and ocular growth in C57BL/6J mice from postnatal day (P) 21 to month 22.</p><p><strong>Results: </strong>The ChT gradually increased with age, with the thickest region in the para-optic nerve head and thinning outward, and the temporal ChT was globally thicker than the nasal ChT. Retinal thickness remained stable until 4 months and subsequently decreased. The average spherical equivalent refraction error was -4.81 ± 2.71 diopters (D) at P21, which developed into emmetropia by P32, reached a hyperopic peak (+5.75 ± 1.38 D) at P82 and returned to +0.66 ± 1.86 D at 22 months. Central corneal thickness, anterior chamber depth, lens thickness, and axial length (AL) increased continuously before 4 months, but subsequently exhibited subtle changes. Vitreous chamber depth decreased with lens growth. ChT was correlated significantly with the ocular parameters (except for retinal thickness) before the age of 4 months, but these correlations diminished after 4 months. Furthermore, for mice younger than 4 months, the difference in the ChT, especially temporal ChT, between the two eyes contributed most to that of axial length and spherical equivalent refraction error.</p><p><strong>Conclusions: </strong>Four months could be a watershed age in the growth of mouse eyes. Large-span temporal recordings of refraction, ocular dimensions, and choroidal changes provided references for the study of the physiological and pathological mechanisms responsible for myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"26"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465682","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":"ROCK Inhibitor Enhances Neurite Outgrowth In Vitro and Corneal Sensory Nerve Reinnervation In Vivo.","authors":"Beverly A Karpinski, Sonali Pal-Ghosh, Himani Datta-Majumdar, Shelly Dimri, Soneha Datta, Mary Ann Stepp","doi":"10.1167/iovs.65.12.31","DOIUrl":"10.1167/iovs.65.12.31","url":null,"abstract":"<p><strong>Purpose: </strong>The intraepithelial corneal nerves are essential to corneal health. Rho kinase or ROCK inhibitors (RIs) have been reported to play a role in neuron survival after injury. Here we assess integrin and extracellular matrix expression in primary mouse neurons and determine whether treating cells with RI impacts neurite outgrowth in vitro and reinnervation after trephine and debridement injury in mice in vivo.</p><p><strong>Methods: </strong>Cocultures of human corneal limbal epithelial cells and E11.5 mouse trigeminal neurons and neurons alone were grown on glass coverslips. High-resolution imaging was performed to localize integrins and laminin on neurons and to determine whether RI impacts neurite outgrowth in vitro and in vivo after both 1.5-mm trephine and 1.5-mm debridement injuries.</p><p><strong>Results: </strong>Several integrin α (α3, α6, αv) chains as well as β4 integrin are expressed on neuron axons and growth cones in cocultures. RI treatment of isolated neurons, cocultures, and in conditioned media increases neurite outgrowth. In vivo, RI positively impacts sensory nerve reinnervation after trephine and debridement injury.</p><p><strong>Conclusions: </strong>These studies are the first to demonstrate expression of β4 integrin on trigeminal sensory neurons and preferential adhesion of neurons to the laminin-enriched matrices found in footprints deposited by human corneal limbal epithelial cells. In addition, we also document for the first time the positive impact of RI on neurite outgrowth in vitro and reinnervation in vivo.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"31"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465686","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":"Critical Impact of Working Distance on OCT Imaging: Correction of Optical Distortion and Its Effects on Measuring Retinal Curvature.","authors":"Yong Woo Kim, Glen P Sharpe, Julia Siber, Ralf Keßler, Jörg Fischer, Tilman Otto, Balwantray C Chauhan","doi":"10.1167/iovs.65.12.10","DOIUrl":"10.1167/iovs.65.12.10","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the impact of working distance (WD) on optical distortion in optical coherence tomography (OCT) imaging and to evaluate the effectiveness of optical distortion correction in achieving consistent retinal Bruch's membrane (BM) layer curvature, regardless of variations in WD.</p><p><strong>Methods: </strong>Ten subjects underwent OCT imaging with four serial macular volume scans, each employing distinct WD settings adjusted by balancing the sample and reference arm of the OCT interferometer (eye length settings changed). Either of two types of 30° standard objectives (SOs) was used. A ray tracing model was used to correct optical distortion, and BM layer curvature (represented as the second derivative of the curve) was measured. Linear mixed effects (LME) modeling was used to analyze factors associated with BM layer curvature, both before and after distortion correction.</p><p><strong>Results: </strong>WD exhibited significant associations with axial length (β = -1.35, P < 0.001), SO type (P < 0.001), and eye length settings (P < 0.001). After optical distortion correction, the mean ± SD BM layer curvature significantly increased from 16.80 ± 10.08 µm-1 to 49.31 ± 7.50 µm-1 (P < 0.001). The LME model showed a significant positive association between BM layer curvature and WD (β = 1.94, P < 0.001). After distortion correction, the percentage change in BM layer curvature due to a 1-mm WD alteration decreased from 9.75% to 0.25%.</p><p><strong>Conclusions: </strong>Correcting optical distortion in OCT imaging significantly mitigates the influence of WD on BM layer curvature, enabling a more accurate analysis of posterior eye morphology, especially when variations in WD are unavoidable.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380867","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":"Retinal Organoid Microenvironment Enhanced Bioactivities of Microglia-Like Cells Derived From HiPSCs.","authors":"Mei-Ling Gao, Tong-Yu Wang, Xin Lin, Chun Tang, Mengyao Li, Zhan-Pei Bai, Zhi-Cong Liu, Li-Jun Chen, Qing-Ran Kong, Shao-Hui Pan, Shan-Shan Zeng, Ya Guo, Jian-Qi Cai, Xiu-Feng Huang, Jun Zhang","doi":"10.1167/iovs.65.12.19","DOIUrl":"10.1167/iovs.65.12.19","url":null,"abstract":"<p><strong>Purpose: </strong>Microglia-like cells derived from stem cells (iMG) provide a plentiful cell source for studying the functions of microglia in both normal and pathological conditions. Our goal is to establish a simplified and effective method for generating iMG in a precisely defined system. Additionally, we aim to achieve functional maturation of iMG through coculture with retinal organoids.</p><p><strong>Methods: </strong>In this study, iMG were produced under precisely defined conditions. They were subjected to LPS and poly IC stimulation. Additionally, we examined distinct phenotypic and functional variances between iMG and HMC3, a commonly used human microglia cell line. To investigate how the retinal cell interaction enhances microglial properties, iMG were cocultured with retinal organoids, producing CC-iMG. We performed RNA sequencing, electrophysiological analysis, and transmission electron microscope (TEM) to examine the maturation of CC-iMG compared to iMG.</p><p><strong>Results: </strong>Our results demonstrated that iMG performed immune-responsive profiles closely resembling those of primary human microglia. Compared to HMC3, iMG expressed a higher level of typical microglial markers and exhibited enhanced phagocytic activity. The transcriptomic analysis uncovered notable alterations in the ion channel profile of CC-iMG compared to iMG. Electrophysiological examination demonstrated a heightened intensity of inward- and outward-rectifying K+ currents in CC-iMG. Furthermore, CC-iMG displayed elevated numbers of lysosomes and mitochondria, coupled with increased phagocytic activity.</p><p><strong>Conclusions: </strong>These findings contribute to advancing our understanding of human microglial biology, specifically in characterizing and elucidating the functions of CC-iMG, thereby offering an in vitro microglial model for future scientific research and potential clinical applications in cell therapy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"19"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400281","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":"Severity Stratification of Coronary Artery Disease Using Novel Inner Ellipse-Based Foveal Avascular Zone Biomarkers.","authors":"Natasa Jeremic, Maximilian Pawloff, Dmitrii Lachinov, Stephanie Rokitansky, Matthias Hasun, Franz Weidinger, Andreas Pollreisz, Hrvoje Bogunovic, Ursula Schmidt-Erfurth","doi":"10.1167/iovs.65.12.15","DOIUrl":"10.1167/iovs.65.12.15","url":null,"abstract":"<p><strong>Purpose: </strong>Given the similarities between the retinal and coronary microvasculature, the retina holds promising potential to serve as a non-invasive screening tool for coronary artery disease (CAD). We aimed to develop novel inner ellipse-based metrics and discern whether foveal avascular zone (FAZ) alterations can serve as indicators for CAD presence and severity.</p><p><strong>Methods: </strong>Patients admitted to the Department of Cardiology who underwent coronary angiography were included. This resulted in an inclusion of 212 patients, of which 73 had no CAD. During the same visit, 6 × 6-mm (nominal size) fovea-centered optical coherence tomography angiography images of both eyes were acquired. The Gensini score (GS) was utilized to quantify CAD severity. Six known FAZ shape metrics were assessed and three novel biomarkers based on the inner ellipse were defined: absolute inner ellipse difference, Hausdorff distance, and Chamfer distance.</p><p><strong>Results: </strong>Eight out of nine metrics showed significant associations with the GS in the left eye. However, significant differences across three CAD severity groups were only demonstrated by the novel metrics. Utilizing the Chamfer distance, age, and sex, patients with and without CAD could be distinguished with an average area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.84-0.95). Moreover, three CAD severity groups could be discerned with a macro average AUC of 0.77 (95% CI, 0.72-0.84).</p><p><strong>Conclusions: </strong>A comprehensive assessment of FAZ shape descriptors was performed, and a strong association with CAD was found. The inner ellipse-based biomarkers especially demonstrated high predictive abilities for CAD presence and severity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390592","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}