LingQiao Li, Han Bao, ErChi Zhang, ShuTing Wu, XiaoYang Jiang, YuJia Xiao, ShiJing Fan, YiXin Luo, YunYun Huang, Pei Zhang, Michael Swain, Ahmed Elsheikh, ShiHao Chen, XiaoBo Zheng
{"title":"Effect of corneal cross-linking on biomechanical properties of swollen rabbit corneas.","authors":"LingQiao Li, Han Bao, ErChi Zhang, ShuTing Wu, XiaoYang Jiang, YuJia Xiao, ShiJing Fan, YiXin Luo, YunYun Huang, Pei Zhang, Michael Swain, Ahmed Elsheikh, ShiHao Chen, XiaoBo Zheng","doi":"10.1016/j.exer.2024.110191","DOIUrl":"10.1016/j.exer.2024.110191","url":null,"abstract":"<p><p>Corneal cross-linking (CXL) is an effective method to prevent the progression of keratoconus. CXL combined with hypotonic riboflavin solution is a modified treatment for thin corneas, which are deemed to be below the safe thickness threshold. In this study, rabbit corneas were subjected to different hydration levels using different osmolarity of riboflavin dextran solutions before CXL. Inflation testing was performed to evaluate the corneal biomechanical stiffening effect of hypotonic riboflavin solutions crosslinking. One-month post-CXL, the stromal demarcation line depth (DLD) and the biomechanical property parameter - tangent modulus (Et) - were measured. All CXL groups showed higher Et than the corresponding Ctrl groups (all P < 0.001), however, the Et values showed no statistical differences between the CXL-ed groups with different hydration levels (all P > 0.05). The relative depth ratio of DLD to total corneal thickness (TCT) did not show significant differences (P > 0.05), while the DLD was statistically different in three CXL groups (P < 0.001). The research suggested that riboflavin solutions with different osmolarities are suitable for preoperative swelling of corneas with different thickness ranges. Furthermore, crosslinking with hypotonic riboflavin solutions has no significant effect on corneal biomechanical improvement under a certain degree of hydration.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110191"},"PeriodicalIF":3.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767658","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}
Natalia Castro, Juan S Peña, Richard Cliver, François Berthiaume, Maribel Vazquez
{"title":"Estradiol impacts Müller glia and endothelial cell responses in hyperglycemic microenvironments with advanced glycation end products.","authors":"Natalia Castro, Juan S Peña, Richard Cliver, François Berthiaume, Maribel Vazquez","doi":"10.1016/j.exer.2024.110185","DOIUrl":"10.1016/j.exer.2024.110185","url":null,"abstract":"<p><p>Diabetic retinopathy is a leading cause of vision loss in working adults, with disproportionate impact on women with lowered estrogen. Sex hormones and their receptors are significant to neuroprotection of the inner blood-retinal barrier (iBRB), a tissue that regulates transport across the neuroretina and vasculature. Moreover, high glucose levels in diabetes lead to the formation of advanced glycation end products (AGEs), which promote inflammation and iBRB breakdown to result in vision loss. This study examined the effects of supplemental estradiol on cell reactivity and cell barrier resistance within an in vitro model of hyperglycemia. Changes in morphology and expression of reactive oxygen species were examined when cells were exposed to a hyperglycemic medium containing AGEs, with and without supplemental estradiol. Cell morphology was assessed via changes in cell area and cell shape index, while intracellular ROS levels were measured using a ROS-sensitive dye. In addition, trans endothelial resistance (TEER) assays were used to measure changes in cell barrier function in response to hyperglycemic conditions, with and without supplemental estradiol. Results show that ROS levels in Müller glia in hyperglycemic conditions significantly decreased in response to supplemental estradiol. The estradiol further increased the resistivity of Müller glia and endothelial cell barriers cultured in high glucose and AGEs. This project illustrates the restorative effects of estradiol in collective responses of cell barriers formed by endothelial cells and Müller glia.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110185"},"PeriodicalIF":3.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767595","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":"Integrative analysis and knowledgebase construction of key candidate genes and pathways in age-related macular degeneration.","authors":"Dongyue Wang, Tong Tang, Yayi Wang, Jing Zhao, Bairong Shen, Ming Zhang","doi":"10.1016/j.exer.2024.110177","DOIUrl":"10.1016/j.exer.2024.110177","url":null,"abstract":"<p><p>Age-related macular degeneration is a retinal disease that severely impacts vision in the older population. Its gene-related heterogeneity has not been fully studied, increasing the burden of precise treatment, prevention and prognosis. Genetic variation and related information were collected, annotated and expanded from multiple related websites, and all the data were integrated into the online platform AMDGKB. Users can visit this database via the following link: http://amdgd.bioinf.org.cn/for their personalized applications knowledge-guided modeling and applications. This study also explored the heterogeneity of ethnicity and AMD subtypes via genetic variation, functional enrichment analysis and protein‒protein interactions. These results suggest that VEGFA, MT2A, CCL2 and SERPINF1 play different roles in the development of AMD in different ethnic groups. The enrichment analysis also revealed differences in the pathogenesis pathways of different ethnic groups and AMD subtypes. This study highlights that genetic heterogeneity needs to be considered in the process of diagnosis and treatment. AMDGKB provides information for investigating the transformation of genetic variation during AMD progression, as well as for future personalized applications in the diagnosis and prognosis of AMD.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110177"},"PeriodicalIF":3.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767601","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}
Rongrong Gao , Yuyan Huang , Aodong Chen , Qingqing Jiang , Shengnan Ding , Keith M. Meek , Qinmei Wang , A-Yong Yu , Jinhai Huang
{"title":"Comparison of rose bengal-green light scleral crosslinking in rabbit eyes using different infiltration protocols - An Ex Vivo study","authors":"Rongrong Gao , Yuyan Huang , Aodong Chen , Qingqing Jiang , Shengnan Ding , Keith M. Meek , Qinmei Wang , A-Yong Yu , Jinhai Huang","doi":"10.1016/j.exer.2024.110183","DOIUrl":"10.1016/j.exer.2024.110183","url":null,"abstract":"<div><div>Different concentrations and infiltration times of rose bengal (Rb) were assessed for their impact on penetration depth and crosslinking efficacy in rabbit sclera. Fresh rabbit eyes were used. Rb solution with concentrations of 0.1%–0.9% were applied for 5–30 min to infiltrate the sclera. The penetration depth of Rb was observed with confocal microscopy. After infiltration, the sclera was irradiated by green light for crosslinking. The sclera's biomechanical stiffness and the resistance to enzyme digestion post-treatment were evaluated. Histopathological analysis and transmission electron microscopy were performed to observe the morphology. As the infiltration time increased, the penetration depth and the fluorescence intensity of the Rb in sclera increased. After 32 h, 48.6% of the scleral tissue was undissolved in the 0.5% Rb-10min group, followed by the 0.1% Rb-20min group (13.8%) and 0.05% Rb-30min group (7.7%). At 8% strain, the Young's modulus of the 0.05%Rb-30min, the 0.1% Rb-20min and the 0.5% Rb-10min group were respectively 1.77, 2.45 and 3.19 times greater than that of the untreated group. There were no morphological differences between the experimental group and the untreated group. RG-SXL significantly increased the diameter of large collagen fibers in the middle and inner layers of the sclera. Ultimately, 0.5% Rb infiltration for 10 min achieves an appropriate infiltration depth and crosslinking effect, and may thus be a feasible schedule for scleral crosslinking.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110183"},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750270","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":"UPLC-MS/MS-based serum metabolomics analysis for comprehensive pathological myopia profiling.","authors":"Xin Liu, Yue Wu, Yuying Liu, Wenzhe Qian, Liandi Huang, Yixiang Wu, Bilian Ke","doi":"10.1016/j.exer.2024.110152","DOIUrl":"10.1016/j.exer.2024.110152","url":null,"abstract":"<p><p>Pathological myopia (PM) is associated with ocular morbidities that cause blindness. PM often occurs in eyes with high myopia (HM) while they are distinctly different. Identifying the differences in metabolites and metabolic pathways between patients with PM and HM may provide information about the pathogenesis of PM, which is currently unknown. This study aimed to reveal the comprehensive metabolic alterations associated with PM. Thirty patients with PM, 27 with simple HM and 27 with low myopia (LM) were enrolled in this study. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was performed, and a Venn diagram was generated to explore the overlapping differential metabolites and enriched pathways between each set of two groups. The area under the receiver operating characteristic curve (AUC) was computed to assess the discrimination capacity of each metabolite marker. A total of 134, 125 and 81 differential metabolites were identified in each comparison. Thirty-two differential metabolites were overlapped between the PM vs HM comparison and the PM vs LM comparison. Of these 32 metabolites, 16 were common to all three comparisons; among these metabolites, high levels of 4-hydroxy-l-glutamic acid and low levels of succinic semialdehyde and 2,3-dinor-8-iso prostaglandin F2α appeared to be risk factors for PM. The remaining 16 metabolites were shared only between the PM versus HM and PM versus LM comparisons, most of which are lipid molecules. Pathway analysis revealed that alanine, aspartate and glutamate metabolism was the key metabolic pathway altered in PM patients. Overall, significant differences in the metabolites and metabolic pathways were observed in patients with PM. The metabolic differences identified in this study included differential factors between PM and HM patients, addressing current gaps in PM research. These findings provide a novel perspective of the molecular mechanism of PM.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110152"},"PeriodicalIF":3.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738896","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}
Lei Lin, Lili Liang, Liming Xu, Yu Zheng, Hanwen Guo, Bei Zhang, Yun-E Zhao
{"title":"Heat stress regulates the migration and proliferation of lens epithelial cells through ferroptosis and NCOA4-FTH1 interaction.","authors":"Lei Lin, Lili Liang, Liming Xu, Yu Zheng, Hanwen Guo, Bei Zhang, Yun-E Zhao","doi":"10.1016/j.exer.2024.110182","DOIUrl":"10.1016/j.exer.2024.110182","url":null,"abstract":"<p><p>Posterior capsule opacification (PCO) due to the proliferation and migration of lens epithelial cells (LECs) is the main complication after surgery. Heat stress has demonstrated impressive results in halting cell proliferation and migration, while also facilitating cell death. This study aimed to investigate the role and mechanism of ferroptosis in the proliferation and migration of LECs under heat stress. CCK-8 assays, scratch assays, and transcriptome analysis were used to evaluate the impact of temperature on human lens epithelial cells (HLECs) and explore the potential mechanisms. The role of ferroptosis in the proliferation of HLECs induced by heat was investigated using the ferroptosis inhibitor Fer-1 and siRNA-mediated NCOA4 protein interference. Fluorescence staining and Western blot experiments were used to detect the expression of Fe<sup>2+</sup>, reactive oxygen species (ROS), and ferroptosis-related proteins NCOA4, FTH1, and SLC3A2. The results of CCK-8 assays, scratch assays, and transcriptome analysis demonstrated significant thermal effects on HLEC behavior. After heat treatment, there were significant changes in the fluorescence expression of Fe<sup>2+</sup> and ROS in the HLECs and lens explant. In addition, the expression of NCOA4, FTH1, and SLC3A2 also changed significantly. Using Fer-1 or NCOA4 siRNA-mediated interference restored cell viability decreased by thermal stress. Furthermore, interference with NCOA4 protein effectively restored the expression of Fe<sup>2+</sup>, ROS, and FTH1. In conclusion, heat stress has a significant effect on LECs by regulating ferroptosis and the interaction between NCOA4 and FTH1 proteins play an important role.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110182"},"PeriodicalIF":3.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715800","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}
Miaomiao Chi , Yaning Zhao , Bowei Yuan , Zifeng Qiu , Rongmei Peng , Jing Hong
{"title":"MiR-23a-3p targets PTEN as a novel anti-ferroptosis regulator in Fuchs endothelial corneal dystrophy","authors":"Miaomiao Chi , Yaning Zhao , Bowei Yuan , Zifeng Qiu , Rongmei Peng , Jing Hong","doi":"10.1016/j.exer.2024.110180","DOIUrl":"10.1016/j.exer.2024.110180","url":null,"abstract":"<div><div>Fuchs endothelial corneal dystrophy (FECD) is the leading cause of keratoplasty without drug treatment. Research indicated that oxidative stress and lipid peroxidation play significant roles in FECD. However, the underlying pathogenesis and potential treatment remain poorly understood. We analyzed the mRNA expression of FECD using the GEO database (GSE171830). Utilizing the STRING database and Cytoscape's MCODE plugin, we identified hub genes that intersect with ferroptosis-related genes listed in FerrDb. FECD cell and animal models were developed, induced by Ultraviolet A exposure. We assessed ferroptosis by measuring GPX4 expression and ROS fluorescence intensity. MiR-23a-3p was compared between FECD model and normal control, and the target gene PTEN was confirmed through Western blot and dual-luciferase reporter assays. Treatment with PTEN, PI3K, Akt, and mTOR inhibitors provided insights into the role of the PTEN/PI3K/Akt/mTOR pathway in FECD model. Corneal endothelium and cellular structure were evaluated before and after delivery of miR-23a-3p. Bioinformatics analysis of the GSE171830 revealed the top five hub genes: TP53, PTEN, EGFR, EPAS1, and IL-1β. Ferroptosis is the predominant mechanism in FECD pathogenesis, distinct from apoptosis and necrosis. We uncovered a protective role for miR-23a-3p in corneal endothelial cells (CEnCs), mitigating ferroptosis by downregulating PTEN. Corroborating this, bpV (a PTEN inhibitor) was found to attenuate ferroptosis in CEnCs. Mechanistically, PTEN inhibition coupled with sustained PI3K/Akt/mTOR pathway activation emerged as a protective strategy against ferroptosis in CEnCs. Ferroptosis contributes to FECD pathogenesis, and targeted delivery of miR-23a-3p as a ferroptosis inhibitor may offer therapeutic potential by regulating PTEN/PI3K/Akt/mTOR signaling.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110180"},"PeriodicalIF":3.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709697","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}
Huanhuan Ge , Guohu Di , Peirong Song , Wenshuo Han , Peng Chen , Ye Wang
{"title":"Role of vitamin A on the ocular surface","authors":"Huanhuan Ge , Guohu Di , Peirong Song , Wenshuo Han , Peng Chen , Ye Wang","doi":"10.1016/j.exer.2024.110179","DOIUrl":"10.1016/j.exer.2024.110179","url":null,"abstract":"<div><div>Vitamin A is an essential fat-soluble vitamin that cannot be endogenously synthesized by the human body. Retinoic acid (RA) is the biologically active form of vitamin A. Utilizing both nuclear and non-nuclear receptor-mediated pathways, RA plays a crucial role in regulating various biological processes, including apoptosis, differentiation, and anti-inflammatory properties within the cornea and conjunctiva. In addition, RA has been demonstrated to exert a significant influence on anti-tumor mechanisms. Disruption of RA signaling can result in corneal defects, anophthalmia, and microphthalmia. However, the beneficial effects of RA are only observed when it is administered at appropriate dosages, and higher doses have an adverse impact. Ocular abnormalities are often early indicators of a vitamin A deficiency. The lacrimal gland secretes vitamin A onto the ocular surface, where it is metabolized into RA via two sequential steps. This article provides a comprehensive overview of how vitamin A is transformed and transported from the intestine to the ocular surface, ultimately contributing to the maintenance of the normal physiological function of the ocular surface.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110179"},"PeriodicalIF":3.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142705792","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}
Lin Wang , Yangbin Ji , Haibo Mei , Xin Gong , Huachun Miao , Zaiman Zhu , Jian Ding
{"title":"Electroacupuncture improves V1 cortex synaptic plasticity via the CREB/BDNF/TrkB pathway in juvenile rats with monocular deprivation","authors":"Lin Wang , Yangbin Ji , Haibo Mei , Xin Gong , Huachun Miao , Zaiman Zhu , Jian Ding","doi":"10.1016/j.exer.2024.110169","DOIUrl":"10.1016/j.exer.2024.110169","url":null,"abstract":"<div><div>The present study aims to investigate the impact of the CREB/BDNF/TrkB signaling pathway on synaptic plasticity in the visual cortex of juvenile amblyopic rats that have undergone monocular deprivation (MD). This study involved sixty 2-week-old Sprague-Dawley (SD) juvenile rats, which were not specified by gender. In the first part of the study, 24 rats were randomized into control and MD groups; In the second part, 36 rats were randomized into MD, electroacupuncture (EA) and EA + CREB antagonist (666–15) groups. The MD model was established using the monocular suture method. 14 d after monocular suture, EA treatment was started for 30 min daily, at a frequency of 2–10 Hz and an intensity of 1 mA, for 2 weeks. According to the results from part 1, the P100 wave latency in the MD group was prolonged, and its amplitude was lower compared to the control group. Additionally, the neuron number in the V1 cortex of the MD group decreased, along with reduced expression levels of CREB, BDNF, p-TrkB, and the key plasticity proteins PSD95 and SYN. In part 2, EA treatment significantly increased the electrophysiological activity of neurons in V1 cortex, shortened the latency of P100 peaks to varying degrees, increased the amplitude significantly, and restored the morphology and structure of neurons to normal levels; The expression of synaptic proteins PSD95 and SYN, as well as the expression of signaling molecules CREB, BDNF, and p-TrkB proteins were increased. However, the effects of EA were reversed when the specific CREB inhibitor 666–16 was administered. These data indicate that EA enhances the expression of V1 cortical synaptic plasticity-related proteins by regulating the expression of CREB/BDNF/TrkB signaling pathway, thereby enhancing V1 neural synaptic plasticity and reversing the effects of MD on visual acuity.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"250 ","pages":"Article 110169"},"PeriodicalIF":3.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692847","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}