{"title":"Optic Nerve Morphology Influences Structure-Function Relationship in Early Glaucoma With and Without High Myopia.","authors":"Jinpeng Yang, Yangjiani Li, Qi Zhang, Simei Zeng, Haishun Huang, Caiqing Wu, Zhe Liu, Jiahui Tang, Siting Wu, Yuze Chen, Yehong Zhuo, Yangfan Yang, Yiqing Li","doi":"10.1167/iovs.66.4.18","DOIUrl":"10.1167/iovs.66.4.18","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to determine the influence of optic nerve head (ONH) rotation and tilt on the structure-function (S-F) relationship differences between early open-angle glaucoma (OAG) with and without high myopia (HM).</p><p><strong>Methods: </strong>A total of 164 eyes, including 69 early highly myopic glaucoma (HMG) eyes, 60 early OAG eyes, and 35 healthy HM eyes, were included. All the eyes underwent spectral-domain optical coherence tomography, standard automated perimetry, and fundus photography simultaneously. S-F relationships were analyzed by comparing the peripapillary retinal nerve fiber layer thickness (pRNFLT) to the corresponding visual field sensitivity loss (VFSL) according to the Garway-Heath map. Linear regression analyses were used to evaluate the relationship between ONH rotation and tilt with pRNFLT and VFSL.</p><p><strong>Results: </strong>Multivariate regression analysis demonstrated that the ovality index was associated with nasal (P = 0.014) pRNFLT in OAG eyes and with nasal (P < 0.001), temporal (P = 0.012), and superior nasal (P = 0.015) pRNFLT in healthy HM eyes, but not in HMG eyes. Moreover, ONH rotation was significantly associated with inferior nasal (P = 0.013) pRNFLT in HMG eyes and with inferior temporal (P = 0.029) and inferior nasal (P = 0.036) pRNFLT in healthy HM eyes, whereas no associations were observed in OAG eyes. The strongest relationship between pRNFLT and VFSL for HMG and OAG were found in the inferior temporal (R = 0.567) and superior temporal sector (R = 0.638), respectively. However, no significant relationships were observed in healthy HM eyes (all P > 0.05).</p><p><strong>Conclusions: </strong>Optic disc rotation and tilt may affect the distribution of the pRNFL in HM eyes with or without glaucoma, resulting in abnormal correspondence between structure and function. The analysis of the S-F relationship in the inferior temporal sector could be a valuable factor in assessing HMG eyes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803247","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}
Min Gao, Yukun Guo, Tristan T Hormel, Jie Wang, Elizabeth White, Dong-Wouk Park, Thomas S Hwang, Steven T Bailey, Yali Jia
{"title":"Nonperfused Retinal Capillaries-A New Method Developed on OCT and OCTA.","authors":"Min Gao, Yukun Guo, Tristan T Hormel, Jie Wang, Elizabeth White, Dong-Wouk Park, Thomas S Hwang, Steven T Bailey, Yali Jia","doi":"10.1167/iovs.66.4.22","DOIUrl":"10.1167/iovs.66.4.22","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to develop a new method to quantify nonperfused retinal capillaries (NPCs) and evaluate NPCs in eyes with AMD and diabetic retinopathy (DR).</p><p><strong>Methods: </strong>We averaged multiple registered optical coherence tomography (OCT)/OCT angiography (OCTA) scans to create high-definition volumes. The deep capillary plexus slab was defined and segmented. A developed deep learning denoising algorithm removed tissue background noise from capillaries in en face OCT/OCTA. The algorithm segmented NPCs by identifying capillaries from OCT without corresponding flow signals in OCTA. We then investigated the relationships between NPCs and known features in AMD and DR.</p><p><strong>Results: </strong>The segmented NPC achieved an accuracy of 88.2% compared to manual grading of NPCs in DR. Compared to healthy controls, both the mean number and total length (mm) of NPCs was significantly increased in AMD and DR eyes (P < 0.001, P < 0.001). Compared to early and intermediate AMD, the number and total length of NPCs were significantly higher in advanced AMD (number: P < 0.001, P < 0.001; total length: P = 0.002, P = 0.003). Geography atrophy, macular neovascularization, drusen volume, and extrafoveal avascular area (EAA) significantly correlated with increased NPCs (P < 0.05). In DR eyes, NPCs correlated with the number of microaneurysms and EAA (P < 0.05). The presence of fluid did not significantly correlate with NPCs in AMD and DR.</p><p><strong>Conclusions: </strong>A deep learning-based algorithm can segment and quantify retinal capillaries that lack flow using colocalized OCT/OCTA. This new biomarker may be useful in AMD and DR in predicting progression of these diseases.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811334","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":"Multidimensional Functional Phenotyping Based on Photoreceptor-Directed Temporal Contrast Sensitivity Defects in Inherited Retinal Diseases.","authors":"Cord Huchzermeyer, Katarina Stingl, Jan Kremers","doi":"10.1167/iovs.66.4.25","DOIUrl":"https://doi.org/10.1167/iovs.66.4.25","url":null,"abstract":"<p><strong>Purpose: </strong>To identify patterns of functional defects in perifoveal photoreceptor-directed temporal contrast sensitivities (tCSs) in patients with inherited retinal diseases.</p><p><strong>Methods: </strong>We retrospectively studied patients with RP1L1-associated occult macular dystrophy (OMD), Stargardt disease (STGD), and RP. Photoreceptor-directed tCS directed at L-, M-, S-cones and rods at different temporal frequencies were measured using a four-primary LED-stimulator with an annular test field (2° inner diameter and 12° outer diameter). Mean defects (MDs) were calculated by subtracting sensitivities from age-correlated normal values and averaging defects in frequency ranges where single postreceptoral pathways mediate flicker detection. Each patient was characterized by 6 MD values (one value each for S-cones [SMD] rods [RMD]; two values each for L- [LMDlow/high] and M-cones [MMDlow/high], where low refers to 1-6 Hz and high to 8-20 Hz temporal frequency ranges). Groups of similar phenotypes were identified with (supervised) decision trees and (unsupervised) hierarchical classification trees (based on nearest neighbors) and compared with the clinical diagnoses.</p><p><strong>Results: </strong>The pruned decision tree used RMD for separating RP/STGD from normal/OMD, LMDlow for separating OMD from normal, and SMD for discriminating between RP and STGD. The accuracy was 66%. The hierarchical tree (independent of clinical diagnosis) was cut to four clusters, resulting in one cluster containing mainly normal participants, one cluster with severe L- and M-cone defects caused by OMD or STGD, one cluster with severe rod defects (4/5 with RP) and a large cluster with intermediate rod and cone defects that was dominated by RP and STGD patients.</p><p><strong>Conclusions: </strong>LMDlow, SMD, and RMD were the most important parameters. Photoreceptor-directed tCSs allow sophisticated functional phenotyping of inherited retinal diseases and complement other structural and functional parameters for genotype-phenotype correlations.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"25"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013183","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}
Jing-Xia Liu, Abraha Kahsay, Nils Dennhag, Jonas von Hofsten, Fatima Pedrosa Domellöf
{"title":"Multiterminal En Plaque Motor Endplates in Extraocular Muscles Are Conserved Across Vertebrate Species.","authors":"Jing-Xia Liu, Abraha Kahsay, Nils Dennhag, Jonas von Hofsten, Fatima Pedrosa Domellöf","doi":"10.1167/iovs.66.4.77","DOIUrl":"https://doi.org/10.1167/iovs.66.4.77","url":null,"abstract":"<p><strong>Purpose: </strong>We have previously described a novel type of multiterminal en plaque motor endplates in the human extraocular muscles (EOMs). This study aimed to investigate whether multiterminal en plaque motor endplates are conserved in EOMs among vertebrates.</p><p><strong>Methods: </strong>The motor endplates were identified with α-bungarotoxin (α-BTx) and antibodies against synaptic proteins and neurofilament in the EOMs of zebrafish, rabbits and mice. Transcriptomic data were re-analyzed to identify acetylcholine receptor (AChR) subunits in EOMs and trunk muscles of wild-type zebrafish at five and 20 months of age.</p><p><strong>Results: </strong>In addition to the two typical types of single en plaque and multiple en grappe motor endplates, the third type of multiterminal en plaque motor endplates were observed in the EOMs of zebrafish, rabbits, and mice. The EOMs of zebrafish showed a significantly higher proportion of myofibers containing multiterminal en plaque motor endplates compared to EOMs of rabbits and mice. RNA sequencing data revealed significantly higher AChR subunits in the zebrafish EOMs compared to trunk muscles.</p><p><strong>Conclusions: </strong>Multiterminal en plaque motor endplates are not exclusive to human EOMs but are also present in the EOMs of other vertebrate species, suggesting a conserved feature of the EOMs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"77"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019213","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}
Matthieu Duot, Sarah Y Coomson, Sanjaya K Shrestha, M V Murali Krishna Nagulla, Yann Audic, Ruteja A Barve, Hongzhan Huang, Carole Gautier-Courteille, Luc Paillard, Salil A Lachke
{"title":"Transcriptome Meta-Analysis Uncovers Cell-Specific Regulatory Relationships in Embryonic, Juvenile, Adult, and Aged Mouse Lens Epithelium and Fibers.","authors":"Matthieu Duot, Sarah Y Coomson, Sanjaya K Shrestha, M V Murali Krishna Nagulla, Yann Audic, Ruteja A Barve, Hongzhan Huang, Carole Gautier-Courteille, Luc Paillard, Salil A Lachke","doi":"10.1167/iovs.66.4.42","DOIUrl":"https://doi.org/10.1167/iovs.66.4.42","url":null,"abstract":"<p><strong>Purpose: </strong>The lens transcriptome has been examined using microarrays and RNA-sequencing (RNA-seq). These omics data are the basis of the bioinformatics web-resource iSyTE that has identified new genes involved in lens development and cataract. The lens predominantly contains epithelial and fiber cells, and yet, presently, iSyTE is based on whole lens data. To gain cell-specific regulatory insights, we meta-analyzed isolated epithelium and fiber transcriptomes from embryonic/postnatal, adult and aged lenses.</p><p><strong>Methods: </strong>Mouse lens epithelium and fiber transcriptome public datasets at embryonic (E) and postnatal (P) stages E12.5, E14.5, E16.5, E18.5, P0.5, P0, P5, P13, and age one month, three months, six months, and two years were analyzed. Microarray or RNA-seq data were analyzed by appropriate methods and compared to other resources (e.g., Cat-Map, CompBio).</p><p><strong>Results: </strong>Across all RNA-seq datasets examined, 2466 genes are differentially expressed between epithelium and fibers, of which 106 are cataract-linked. Gene ontology enrichment validates epithelial and fiber expression, corroborating the meta-analysis. Whole embryonic-body-in silico subtraction and other analyses identify several new high-priority epithelial- and/or fiber-enriched genes (e.g., Casz1, Ell2). Furthermore, new insights into cell-specific regulatory processes at distinct stages are identified (e.g., ribonucleoprotein regulation in E12.5 epithelium). Finally, this data is made accessible at iSyTE (https://research.bioinformatics.udel.edu/iSyTE/).</p><p><strong>Conclusions: </strong>This spatiotemporal transcriptome meta-analysis comprehensively informs on epithelium- and fiber-specific regulatory processes in developing, adult and aged lenses. Notably, it includes the first description of an embryonic stage (i.e., E12.5) representing early primary fiber differentiation, thus informing on the initial transcriptome changes as lens cell-types are readily distinguishable.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"42"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020562","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}
Xingyu Xiao, Jianchun Zhao, Shiqun Lin, Yajie Yang, Wenhui Li, Yan Zhou, Xiao Zhang, Rongping Dai
{"title":"Relationships Between Retinal Vascular Characteristics and Systemic Indicators in Patients With Diabetes Mellitus.","authors":"Xingyu Xiao, Jianchun Zhao, Shiqun Lin, Yajie Yang, Wenhui Li, Yan Zhou, Xiao Zhang, Rongping Dai","doi":"10.1167/iovs.66.4.72","DOIUrl":"https://doi.org/10.1167/iovs.66.4.72","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a deep learning method for vessel segmentation in fundus images, measure retinal vessels, and study the connection between retinal vascular features and systemic indicators in diabetic patients.</p><p><strong>Methods: </strong>We conducted a study on patients with diabetes mellitus (DM) at various stages of diabetic retinopathy (DR) using data from the Joint Asia Diabetes Evaluation (JADE) Register. All participants underwent comprehensive clinical assessments, including anthropometric measurements, laboratory tests, and fundus photography, during each follow-up visit (2.81 average follow-up visits). A custom U-Net deep learning model utilizing a variety of open-source datasets was developed for the segmentation and measurement of retinal vessels. We investigated the relationship between systemic indicators and the severity of DR, analyzing the correlation coefficients between systemic indicators and retinal vascular characteristics.</p><p><strong>Results: </strong>We enrolled a total of 637 patients diagnosed with DM and collected 3575 series of photographs for analysis. Some of the systemic indicators and retinal vascular metrics, including central retinal arteriolar equivalent, central retinal venular equivalent, arteriole-to-venule ratio, and fractal dimension, were significantly correlated with the severity of diabetic retinopathy (P < 0.05). Some physical characteristics, hematological parameters, renal function parameters, metabolism-related parameters, biochemical markers such as folic acid and fasting insulin, liver enzymes, and macrovascular indicators were significantly correlated with certain retinal vascular metrics (P < 0.05).</p><p><strong>Conclusions: </strong>Multiple systemic indicators were identified as significantly associated with the advancement of diabetic retinopathy and retinal vascular metrics. Utilizing deep learning techniques for vessel segmentation and measurement on color fundus photographs can help elucidate the connections between retinal vascular characteristics and systemic indicators.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"72"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002381","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":"Corneal Sensory Nerve Injury Disrupts Lacrimal Gland Function by Altering Circadian Rhythms in Mice.","authors":"Senmao Li, Jingbin Xie, Jiayan Xiang, Ruyu Yan, Jiangman Liu, Qiwei Fan, Liyuan Lu, Jiaxin Wu, Jun Liu, Yunxia Xue, Ting Fu, Zhijie Li","doi":"10.1167/iovs.66.4.40","DOIUrl":"https://doi.org/10.1167/iovs.66.4.40","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the impact of corneal sensory nerve injury on lacrimal gland function, focusing on mechanisms involving the superior salivatory nucleus (SSN), circadian rhythm disruption, immune microenvironment alterations, and the potential for neural regeneration.</p><p><strong>Methods: </strong>A murine model of corneal sensory nerve injury was used to assess lacrimal gland function, with tear secretion measured using the phenol red thread test. Transcriptomic analysis of lacrimal glands examined circadian rhythm and immune-related gene expression. Basic fibroblast growth factor (bFGF) was used to promote corneal nerve regeneration, and its effects on tear secretion and nerve repair were evaluated.</p><p><strong>Results: </strong>Corneal nerve injury resulted in a 35% reduction in tear secretion and significantly impaired SSN activity, as evidenced by a 31% decrease in c-FOS-positive neurons in choline acetyltransferase (ChAT)-expressing neurons. Transcriptomic analysis revealed significant downregulation of immune-related pathways, including Toll-like receptor (TLR), NOD-like receptor (NLR), and T-cell receptor signaling. Circadian rhythm gene expression exhibited phase shifts, with a 2.13-hour delay in peak expression and a substantial change in the number and types of rhythmic genes, which were enriched in different signaling pathways. The bFGF treatment restored tear secretion by 22% and promoted nerve regeneration, although nerve fiber density remained 74% lower than that of controls.</p><p><strong>Conclusions: </strong>Corneal sensory nerve injury disrupts both central and peripheral circadian clock functions in the lacrimal gland, leading to reduced tear secretion and immune dysregulation. These findings highlight the novel role of circadian rhythms and neural-immune interactions in lacrimal gland dysfunction. Neural regeneration strategies, such as bFGF, offer therapeutic potential for dry eye syndrome, providing new directions for clinical intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"40"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997224","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}
Kaiyan Huang, Mi Xia, Qianwen Gong, Kexin Li, Yijie Xu, Hui Wang, Yuzhou Wang, Jiawei Zhou, Liang Hu
{"title":"The Relationship Between Binocular Imbalance and Myopic Shift in Unoperated Eyes After Unilateral SMILE and tPRK.","authors":"Kaiyan Huang, Mi Xia, Qianwen Gong, Kexin Li, Yijie Xu, Hui Wang, Yuzhou Wang, Jiawei Zhou, Liang Hu","doi":"10.1167/iovs.66.4.32","DOIUrl":"https://doi.org/10.1167/iovs.66.4.32","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the relationship between binocular imbalance and myopic shift in unoperated eyes after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures.</p><p><strong>Methods: </strong>This study included 51 participants who had undergone unilateral SMILE (n = 28) or tPRK (n = 23) for at least 3 months. The participants were categorized into stable and myopic shift groups based on the difference between preoperative and postoperative spherical equivalent refractive (SER) errors of unoperated eyes. Psychophysical tests were conducted only at the postoperative follow-up point. Spatial sensory eye dominance was determined by analyzing a binocular orientation combination task at spatial frequencies of 1 and 6 cycles per degree (c/d). A rotating cylinder generated a spontaneous Pulfrich phenomenon to determine the interocular delay at spatial frequencies of 0.95 and 2.95 c/d.</p><p><strong>Results: </strong>The logrBP in the myopic shift group was significantly more negative than in the stable group at 1 c/d (P < 0.01) and 6 c/d (P < 0.01). And logrBP correlated with the difference between preoperative and postoperative SER of the unoperated eye at 1 c/d (rs = 0.513, P < 0.001) and 6 c/d (rs = 0.504, P < 0.001). In the myopic shift group, logrBP was more negative at 6 c/d than at 1 c/d (P = 0.013), but not in the stable group.</p><p><strong>Conclusions: </strong>Patients who experience myopic shift in the unoperated eye after unilateral SMILE or tPRK tend to have stronger sensory eye dominance in that eye, with a more pronounced dominance at higher spatial frequencies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"32"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997226","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}
Pengfei Zhang, Suman K Manna, Mayank Goswami, Robert J Zawadzki, Edward N Pugh
{"title":"A Narrowband 635 nm Autofluorescence Peak in Albino Mouse Eyes Found With Multi-Modal Imaging Reveals the Presence of Protoporphyrin IX in the Choroid.","authors":"Pengfei Zhang, Suman K Manna, Mayank Goswami, Robert J Zawadzki, Edward N Pugh","doi":"10.1167/iovs.66.4.29","DOIUrl":"https://doi.org/10.1167/iovs.66.4.29","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate differences in fundus autofluorescence (AF) spectra of pigmented (C57Bl/6) and albino (Balb/c) mouse retinas.</p><p><strong>Methods: </strong>AF spectra were measured with a scanning laser ophthalmoscope (SLO) with a high-resolution spectrometer. The action spectrum of a 635 nm AF \"spike\" in albino mice was measured to estimate the underlying absorption spectrum. Optical coherence tomography (OCT) and OCT angiography were used to determine the most likely depth location of the source of the AF feature.</p><p><strong>Results: </strong>Two narrowband emission peaks centered at 635 nm and ∼705 nm were observed in the AF spectra of albino (but not pigmented) mouse eyes. The dual-peak emission spectrum of the albino eye was extracted by subtracting a broadband emission that was similar in pigmented and albino mice: the two peaks correspond to emission spectra peaks of protoporphyrin IX, an obligate precursor in the biosynthesis of heme and cytochrome c. The action spectrum of the prominent 635 nm emission component corresponded with the PPIX absorption spectrum. The spatial distribution of the 635 nm emission did not correspond to that of the retinal vasculature but had a pattern more consistent with a choroidal origin.</p><p><strong>Conclusions: </strong>Our results reveal that substantial PPIX is present in the posterior tissues of albino (Balb/c) mouse eyes, and measurable with high-resolution spectral measurements, and suggest that the absence of the narrow band PPIX emission peaks in pigmented eyes arises at least in part from screening by RPE and choroidal melanin.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"29"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997066","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":"Astrocyte-Derived Extracellular Vesicles Alleviate Optic Nerve Injury Through Remodeling of Retinal Microenvironmental Homeostasis.","authors":"Lili Chen, Zhonghao Yu, Senmiao Zhu, Shihan Song, Guanwen He, Zai-Long Chi, Wencan Wu","doi":"10.1167/iovs.66.4.16","DOIUrl":"10.1167/iovs.66.4.16","url":null,"abstract":"<p><strong>Purpose: </strong>Traumatic optic neuropathy (TON) leads to the loss of retinal ganglion cells (RGCs) and results in permanent visual impairment. Protecting and regenerating RGCs is crucial for the treatment of TON. Studies have demonstrated that astrocyte-derived extracellular vesicles (ADEVs) exhibit neuroprotective effects in models of central nervous system (CNS) injury. This study aimed to investigate whether ADEVs have a similar neuroprotective effect on RGCs in an optic nerve crush (ONC) rat model.</p><p><strong>Methods: </strong>ADEVs were collected from primary rat astrocytes, and an ONC model was established to evaluate the effects of ADEVs on retinal structure and visual function using optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and flash visual evoked potential (f-VEP) analysis. Immunofluorescence was used to examine RGCs and investigate reactive gliotic changes. Additionally, miRNA sequencing of ADEVs and retinal mRNA sequencing were performed to identify the potential mechanisms involved.</p><p><strong>Results: </strong>ADEVs protected RGCs from progressive loss and improved visual function. ADEVs also significantly increased the expression of glial fibrillary acidic protein (GFAP) and modulated microglial activation. The miRNAs associated with ADEVs were targeted by neuroprotective signals, such as MAPK, PI3K-AKT, and TNF-α, and through the targeting network generated via retinal mRNA sequencing, we found that potential functional genes, such as THBS1, PAK3, and Gstm1, likely participate in microenvironmental regulation.</p><p><strong>Conclusions: </strong>We discovered that ADEVs play a neuroprotective role in optic nerve injury. Our findings provide a new cell-free therapeutic strategy for optic neuropathy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795501","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}