Experimental eye research最新文献

{"title":"Genetic association of MIR-449B, GCLC, eNOS, SORD, and ENPP1 with diabetic retinopathy","authors":"Huijuan Xu , Lin Fan , Huaichao Luo , Xueming Ju , Huan Li , Shisong Rong , Ye Yuan , Jialing Xiao , Ruifan Zhang , Kaifang Wang , Rong Zou , Fang Hao , Yi Shi , Yu Zhou , Zhenglin Yang , Yijun Liu , Bo Gong","doi":"10.1016/j.exer.2025.110287","DOIUrl":"10.1016/j.exer.2025.110287","url":null,"abstract":"<div><div>Identifying the genetic risk factors of diabetic retinopathy (DR) is essential for discovering the potential pathogenesis of DR. This study determined the association of DR with five single nucleotide polymorphisms (SNPs) specifically in type 2 diabetes mellitus (T2DM) patients, including rs10061133(<em>MIR-449B)</em>, rs17883901(<em>GCLC)</em>, rs2070744(<em>eNOS</em>), rs3759890 (<em>SORD)</em> and rs7754561 (<em>ENPP1).</em> A total of 1433 individuals were enrolled in this study, comprising healthy controls (ctrls = 480), individuals with diabetes mellitus without retinopathy (DNR = 480), non-proliferative DR(NPDR = 378), and proliferative DR(PDR = 95). The five SNPs were genotyped utilizing Mass ARRAY MALDI-TOF technology. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele. We performed a literature search in PubMed published before July 16, 2023. The Newcastle Ottawa Scale was used to evaluate the overall quality of the case-control studies. <strong>Consequently,</strong> we found that there were statistically significant differences between PDR cases and healthy controls for rs10061133 (P = 0.007, OR = 1.59, 95% CI = 1.32–2.23) and rs17883901 (P = 0.020, OR = 1.67, 95% CI = 1.08–2.57), rs17883901 was significantly associated with NPDR (P = 0.023, OR = 1.39, 95% CI = 1.05–1.85), there was a significant association between DR cases and healthy controls (P = 0.048, OR = 1.22, 95% CI = 1.00–1.48) for rs3759890 in the allelic model. DR show no relationships with the other two SNPs compared to healthy controls. In multivariate analyses comparing the DR and DNR groups, rs7754561(A), rs10061133(G), and rs17883901(A) were identified as risk loci for DR in individuals with a duration of diabetes of ≥5 years (P = 0.0023, P = 0.0037, and P = 0.0376, respectively). Furthermore, individuals carrying rs10061133(G) exhibited a higher risk of DR in the hyperglycemic group (glucose ≥8 mmol/L). Secondly, we showed that one polymorphism in <em>eNOS</em> (rs2070744, T > C) showed a suggestive association with DR in the meta-analysis (allelic model:P < 0.05, OR = 1.18, 95% CI: 1.07–1.30, Z = 3.46, I<sup>2</sup> = 34%). Subsequently, including studies that used either healthy subjects or diabetic subjects without DR as controls, the association of <em>eNOS</em> rs2070744 with DR was consistently significant (P = 0.002) and exhibited intermediate heterogeneity (I<sup>2</sup> = 48%). Furthermore, polymorphisms in <em>GCLC</em> (rs17883901) and <em>SORD</em> (rs3759890) were also associated with DR, with P-values of 0.004 (I<sup>2</sup> = 93%) and 0.03 (I<sup>2</sup> = 3%), respectively, suggesting their potential involvement in the disease. <strong>In conclusion,</strong> this study documented that rs10061133(G), rs17883901(A), and rs3759890(G) could be the independent risk factors fo<u>r</u> retinopathy in Chinese patients with T2DM, offering a foundation for genetic risk assessment in clinica","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110287"},"PeriodicalIF":3.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting irreversible cone photoreceptors injury caused by whole-body hyperthermia","authors":"Xufeng Dai ,&nbsp;Fan Ye ,&nbsp;Hao Chen","doi":"10.1016/j.exer.2025.110278","DOIUrl":"10.1016/j.exer.2025.110278","url":null,"abstract":"<div><div>Whole-body hyperthermia (WBH) has been used as an adjunctive strategy for treating malignant and viral diseases<em>.</em> However, WBH can cause toxic reactions in the brain and affect cerebral function. The retina is an extension of the brain. This study concerned about the effects of WBH on murine retinas. Under general anesthesia, the C57BL/6J mice in the WBH group were maintained abdomen-down position on a thermostatic platform, the temperature of which ranged from 40 to 43 °C. Ultimately, murine rectal temperatures reached a recommended high point, approximately 42 °C. However, rectal temperatures of the control mice were maintained within the normal range from 37 to 38 °C. The WBH and sham heating process lasted 2 h. Due to loss of eye blinks during general anesthesia, artificial tears were used to prevent cornea dehydration. 3 days after the WBH, full-field electroretinograms (ERGs) elicited by white-light stimuli showed reduced amplitudes of scotopic and photopic responses. 7 days after the hyperthermia, rod-driven ERG amplitudes were almost normal, but photopic ERG amplitudes were still statistically smaller than the normal values. Under dark adaptation, 35 Hz flicker ERGs confirmed that the change of cone-driven responses is irreversible. Retinal cones of the C57BL/6J mice include middlewave-sensitive (M) and ultraviolet-sensitive (UV) subtypes. Here, both M- and UV-cone ERGs showed abnormally reduced amplitudes at the two time points after the WBH. Further study focused on retinal cone opsins, which are definitive markers of cone subtypes and participate in perception of color light with different wavelengths. Analyzing whole-mounted retinas, the hyperthermia led to lower density (less counts per microscopic field) of M- and UV-cone opsins. The change might imply cone death caused by the WBH. Our study immunohistochemically displayed the hyperthermia-induced retinal injury at the microscope level. There were no abnormal findings in fundus photography and retinal optical coherence tomography imaging. Clinically, measuring cone-driven ERGs is suggested to detect potential retinal neuron injury caused by WBH administration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110278"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Involvement of STAT3 activation in ameliorating all-trans-retinal-induced ferroptosis in photoreceptor-derived 661W cells in vitro","authors":"Chao Chen,&nbsp;Jiuyu Yang,&nbsp;Han Wang,&nbsp;Yutian Lei,&nbsp;Yong Diao","doi":"10.1016/j.exer.2025.110280","DOIUrl":"10.1016/j.exer.2025.110280","url":null,"abstract":"<div><div>Ferroptosis, a form of iron-dependent programmed cell death, has emerged as a critical player in various diseases, including retinal degenerative disorders. Previous studies have highlighted that ferroptosis, triggered by all-<em>trans</em>-retinal (atRAL) accumulation in photoreceptor cells, contributes significantly to the pathogenesis of dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1). However, the underlying molecular mechanisms regulating this process remain poorly understood. In this study, we explore the involvement of signal transducer and activator of transcription 3 (STAT3) in the regulation of atRAL-induced 661W photoreceptor cells (mouse-derived photoreceptor cells) ferroptosis. We found that atRAL treatment induces phosphorylation of STAT3 in 661W photoreceptor cells. Meanwhile, we also discovered that the accumulation of Reactive oxygen species (ROS) induced by atRAL partly contributes to the activation of STAT3 in 661W photoreceptor cells. Importantly, our data suggest that inhibition of STAT3 phosphorylation, resulting in increased lipid peroxidation through upregulation of the acyl-CoA synthetase long-chain family member 4 (<em>ACSL4</em>) and prostaglandin-endoperoxide synthase 2 (<em>PTGS2</em>) gene, exacerbates ferroptosis in atRAL-loaded 661W photoreceptor cells. Additionally, our findings further confirm that STAT3 activator Colivelin may significantly reduce ferroptosis in 661W photoreceptor cells exposed to atRAL by regulating the <em>ACSL4</em> and <em>PTGS2</em> gene. Overall, these results revealed that activated STAT3 mitigates atRAL-induced ferroptosis in photoreceptor cells, possibly by reducing <em>ACSL4</em> and <em>PTGS2</em> gene expression. This pathway highlights the therapeutic potential of STAT3 as a novel target for treating dry AMD and STGD1.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110280"},"PeriodicalIF":3.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetic retinopathy features in lund MetS rats","authors":"María José Canz ,&nbsp;Julia Baguña-Torres ,&nbsp;Jordi Huerta ,&nbsp;Helena Isla-Magrané ,&nbsp;Maddalen Zufiaurre-Seijo ,&nbsp;Anna Salas ,&nbsp;Cristina Hernandez ,&nbsp;Rafael Simó ,&nbsp;José García-Arumí ,&nbsp;Jose Raul Herance ,&nbsp;Patricia Bogdanov ,&nbsp;Anna Duarri","doi":"10.1016/j.exer.2025.110274","DOIUrl":"10.1016/j.exer.2025.110274","url":null,"abstract":"<div><div>The Lund MetS rat (BBDR.cg-<em>Lepr</em>^{<em>db/db</em>}<em>.cp</em>/LundRj) is a novel animal model that has a congenic leptin receptor deficiency (LepR^−/−) and males exhibit a variety of metabolic abnormalities mimicking the human metabolic syndrome, including hyperglycemia, dyslipidemia, severe obesity, and a type 2 diabetes-like condition from 14 weeks of age. However, whether Lund MetS rats (LM rats) develop diabetic retinopathy is still unknown. The purpose is to investigate the features of diabetic retinopathy in this model. In this study, male LM rats aged 15 and 30 weeks were analyzed for pathological retinal changes, including vasculopathy, inflammation, reactive gliosis, oxidative stress, and neurodegeneration features on the retinas by histological, immunohistochemical, and gene and protein expression analysis. Compared with the non-diabetic LM rats, diabetic LM rats, mainly at 30 weeks of age, had a decrease in retinal thickness and loss of retinal ganglion cells and photoreceptors, indicating retinal neurodegeneration. They also presented an increase in VEGF-A expression, <em>Endra, Icam-1, Vcam-1</em>, and <em>Endrb</em> vascular genes, and albumin suggesting neurovascular unit dysfunction. Furthermore, retinas presented reactive gliosis and infiltration of microglia, TNF-α-positive vessels and expressed elevated levels of inflammatory genes <em>Tnf-α, IL-18</em> and <em>IL-6</em>, and oxidative stress markers <em>Sod2</em> and 8-hydroxy-2-deoxyguanosine (8-OHdG). Our results suggest that diabetic LM rats reproduce the early neurodegenerative and altered neuro-vascular features that also occur in the human diabetic eye.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110274"},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382059","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":"Retinoids in lipofuscin granules from retinal pigment epithelium as biomarkers of the damaging effect of ionizing radiation","authors":"Tatiana B. Feldman ,&nbsp;Marina A. Yakovleva ,&nbsp;Mikhail A. Ostrovsky","doi":"10.1016/j.exer.2025.110270","DOIUrl":"10.1016/j.exer.2025.110270","url":null,"abstract":"<div><div>Lipofuscin granules accumulate in the retinal pigment epithelium with age, especially in patients with visual diseases, including progressive age-related macular degeneration. Retinoids (bisretinoids and their oxidation products) are major sources of lipofuscin granule fluorescence. The aim of this work was to analyze the radiation-mediated oxidation of retinoids in lipofuscin granules obtained from the human cadaver eye retinal pigment epithelium. Fluorescent and chromatographic analyses of retinoids were performed before and after irradiation of lipofuscin granules with accelerated protons. The fluorescent properties of chloroform extracts from irradiated lipofuscin granules exhibited an increase in fluorescence intensity in the short-wavelength region of 555 nm. This change is associated with an increase in the quantity of retinoid oxidation cytotoxic products after accelerated proton exposure. The radiation-induced oxidation of retinoids caused a noticeable change in its fluorescent properties allows us to consider this phenomenon as a potential opportunity for non-invasively assessment of the degree of radiation exposure and its relative biological effect in humans. Thus, this research proposes a new strategy for assessing the extent of radiation exposure to humans, which evaluates the effects of ionizing radiation on human eye tissues. This approach is based on the principles of the modern non-invasive method of fundus autofluorescence used in ophthalmology for the diagnosis of the retina and retinal pigment epithelium degenerative diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110270"},"PeriodicalIF":3.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of single-cell and bulk transcriptomics reveals β-hydroxybutyrylation-related signatures in primary open-angle glaucoma","authors":"Qing Dai ,&nbsp;Sijie Zhao ,&nbsp;Juan Li,&nbsp;Ning Li,&nbsp;Aiqin Wang,&nbsp;Ziqing Gao,&nbsp;Yuchen Fan","doi":"10.1016/j.exer.2025.110272","DOIUrl":"10.1016/j.exer.2025.110272","url":null,"abstract":"<div><div>The pathophysiology of primary open-angle glaucoma (POAG), the most prevalent glaucoma type, is poorly understood. Although it is well known that epigenetic factors affect the progression of POAG, the impact of β-hydroxybutyrylation (Kbhb) on POAG remains unknown. Based on POAG-related datasets (GSE27276, GSE4316, and GSE231749) retrieved from the Gene Expression Omnibus (GEO) database, four biomarkers (FABP5, GLS, PDLIM1, and TAGLN) with a diagnostic value for POAG were identified by combining differential expression analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. Immune infiltration analysis demonstrated significant differences in the infiltration abundances of 10 immune cells between POAG and controls, including regulatory T cells, monocytes, and macrophages, with notable positive correlations between TAGLN expression and these immune cells. Subsequently, single-cell analysis revealed that GLS, PDLIM1, and TAGLN were higher expressed in chondrocytes, smooth muscle cells, and endothelial cells. In addition, in vitro cellular experiments and animal models revealed that the TAGLN expression trend was consistent with the data from GSE27276 and GSE4316. In conclusion, TAGLN may play an important role in understanding of the molecular mechanisms of POAG and exploration of therapeutic targets.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"254 ","pages":"Article 110272"},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N6-methyladenosine (m6A) modification regulates HSPA1A and HSPA1B expression in Müller cells under high glucose stress","authors":"Hong Yang ,&nbsp;Jini Qiu ,&nbsp;Xinhan Cui ,&nbsp;Xueling Zhang ,&nbsp;Rongmei Zhou ,&nbsp;Jianjiang Xu ,&nbsp;Ruiping Gu ,&nbsp;Kun Shan","doi":"10.1016/j.exer.2025.110275","DOIUrl":"10.1016/j.exer.2025.110275","url":null,"abstract":"<div><div>Müller cells (MCs) represent the major glial cells that are responsible for maintaining retinal homeostasis. In diabetic retinopathy, Müller cell activation occurs in the initial stages, playing a role in many pathological processes, such as neovascularization, neuronal dysfunction, and inflammatory retinal environment. As the most common RNA modification in eukaryotes, <em>N</em>⁶-methyladenosine (m⁶A) exerts dynamic and reversible control over cellular functions in the context of high glucose (HG) stress. Here, we performed combined m⁶A and RNA sequencing to elucidate the landscape of m⁶A modification in MCs under HG environmental stimuli. The potential functions of aberrant m⁶A peaks and differentially expressed genes were analyzed using bioinformatics analysis. Our findings indicate that m⁶A modification may regulate the expression of heat shock proteins (HSPs) 70 isoforms HSPA1A and HSPA1B, which are stress-inducible chaperones critical for cell survival under adverse conditions, including hyperglycemia. Modulating m⁶A modification may regulate critical gene expression and cellular functions of MCs under HG stress.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110275"},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pigment epithelium-derived factor (PEDF) promotes survival and contraction of myoepithelial cells in lacrimal gland","authors":"Yilan Yin ,&nbsp;Colin James Barnstable ,&nbsp;Xiaomin Zhang ,&nbsp;Xiaorong Li ,&nbsp;Shaozhen Zhao ,&nbsp;Joyce Tombran-Tink","doi":"10.1016/j.exer.2025.110269","DOIUrl":"10.1016/j.exer.2025.110269","url":null,"abstract":"<div><div>PEDF is critical for general health of the ocular surface. In order to study mechanisms of PEDF's action in lacrimal gland (LG) secretion, these visual structures were studied in a PEDF deficient (<em>Pedf</em>^{<em>−/−</em>}) mouse model using biochemical, histochemical, and morphometric analyses. In <em>Pedf</em>^{<em>−/−</em>} animals there were several ocular surface and LG disturbances not seen in controls. Notably, changes in body and LG weight, corneal sensitivity, tear film, ocular surface damage, and size of acini comprising the LG were evident. Survival of myoepithelial cells (MECs) surrounding the acini showed a PEDF survival dependence as there were significant reduction in MEC-specific P63 cells and Bcl2 expression levels, and increased TUNEL positive cells in PEDF deficient mice. Expression levels of the major contractile MEC proteins, α-SMA, calponin, and keratin 14, were also reduced with PEDF gene deletion and MECs contraction apparatus impaired, since oxytocin significantly reduced acinar area in controls but had no effect in PEDF deficient LGs, although the oxytocin receptor (OXTR) was expressed in both PEDF genotypes. These findings suggest that PEDF is essential to MECs survival and contractile function, and tear homeostasis on the ocular surface. Treatment with PEDF is likely to alleviate ocular-related conditions in diseases associated with dry eye as well as promote healthy MEC cell function in other secretory glands of the body.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110269"},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant adeno-associated virus with anti-tumor necrosis factor-alpha in an experimental autoimmune uveitis model","authors":"Baiyi Li ,&nbsp;Chuan Zhao ,&nbsp;Shengjie Guo ,&nbsp;Xueru Li ,&nbsp;Hui Zhang ,&nbsp;Yanan Duan ,&nbsp;Mi Zhang ,&nbsp;Qingqin Tao ,&nbsp;Peiran Zhou ,&nbsp;Xiaorong Li ,&nbsp;Xiaomin Zhang","doi":"10.1016/j.exer.2025.110273","DOIUrl":"10.1016/j.exer.2025.110273","url":null,"abstract":"<div><div>Uveitis treatment is associated with side effects and inconsistent outcomes. Existing treatments often fail to provide targeted and sustained relief; thus, novel therapeutic approaches are needed. Among these, gene therapy using adeno-associated virus (AAV) vectors target specific retinal cells, show low immunogenicity, and demonstrate sustained gene expression, making it a potential advancement in uveitis treatment. Therefore, we utilized a AAV2 system encapsulating encoded anti-tumor necrosis factor-alpha (TNF-α) antibody to assess its efficacy in the treatment of experimental autoimmune uveitis (EAU) in mice. Compared with the AAV2-GFP group, AAV2-ADA-injected mice showed significantly reduced clinical, OCT, and histopathological scores in EAU with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the draining lymph nodes (LN). This study demonstrated the safety and effects of AAV2-ADA in EAU treatment, providing a promising therapeutic strategy for uveitis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"253 ","pages":"Article 110273"},"PeriodicalIF":3.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in vascular resistance with intraocular pressure and damage severity in experimental glaucoma","authors":"Stuart K. Gardiner,&nbsp;Grant Cull,&nbsp;Brad Fortune","doi":"10.1016/j.exer.2025.110271","DOIUrl":"10.1016/j.exer.2025.110271","url":null,"abstract":"<div><div>There is evidence of changes in retinal hemodynamics in both experimental glaucoma and human disease. A major potential confound is that intraocular pressure (IOP) may also be directly affecting vascular resistance and/or the vasodilatory capacity of vessels in the optic nerve head and retina. This is particularly problematic in experimental glaucoma, where chronic IOP elevation is maintained, without the IOP-reducing medications typically used by patients involved in human studies. However, those animal studies remain invaluable, due to the possibility of extensive baseline testing in the knowledge that no glaucomatous loss has commenced, and due to the degree of control that is possible over parameters such as medication regimens. In this study, we aim to assess the impact of chronic IOP elevation on vascular resistance parameters, and separate it from the impact of glaucomatous damage severity. Longitudinal measurements were made using laser speckle flowgraphy before and after unilateral IOP elevation in 31 non-human primates. The pulsatile waveform was extracted and used to calculate the pulsatility index (maximum minus minimum, as a proportion of the mean) and resistivity index (maximum flow minus minimum flow, as a proportion of the maximum), in both the major vessels and the other tissue within the optic nerve head, for an average of 18 time points per animal. The vascular resistance indices increased with IOP at both locations, both in the full dataset, and in the subset of data points restricted to the visit at which IOP first exceeded 30 mmHg until the resistance index reached its maximum for that eye (all p &lt; 0.001). After adjusting for the influence of IOP using coefficients from linear mixed effects models, the resistance indices exhibited non-monotonic relations with damage severity, first increasing from baseline, but then decreasing back to or beyond the normal range in eyes with more severe damage. Further studies are needed to accurately characterize the location and timing of these changes during the course of glaucomatous damage, which would help identify the pathophysiologic processes that are underway at different stages of the disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110271"},"PeriodicalIF":3.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143372184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}