Experimental eye research最新文献

{"title":"Bax expression impacts postnatal retinal vascular development and hyperoxia sensitivity","authors":"Nader Sheibani ,&nbsp;Yanzhi Sang ,&nbsp;Shoujian Wang ,&nbsp;Christine M. Sorenson","doi":"10.1016/j.exer.2024.110107","DOIUrl":"10.1016/j.exer.2024.110107","url":null,"abstract":"<div><div>Apoptosis plays prominent roles during organ development, maturation and homeostasis. In the retina, Bcl-2 family members function through the intrinsic cell death pathway with vital roles during vascular development and hyperoxia-mediated vessel obliteration during oxygen induced ischemic retinopathy (OIR). Bim, a BH3 only protein Bcl-2 family member, binds and activates Bax and/or Bak to facilitate apoptosis. In some systems deletion of both Bax and Bak are required to prevent cell loss, such as regression of ocular hyaloid vasculature. We previously showed Bim expression significantly impacts normal retinal vascular development and sensitivity to hyperoxia. Mice deficient in Bim (Bim^−/−) show increased retinal vascular density and are protected from hyperoxia mediated vessel obliteration. Since Bim activates Bax, here we determined the impact lack of Bax expression has on these processes. Compared to Bax^+/+ mice, retinas from Bax^−/− mice had significantly increased numbers of retinal endothelial cells and pericytes. We also demonstrated that hyperoxia-mediated vessel obliteration during OIR was significantly decreased in the absence of Bax. Although the increased endothelial cell numbers were comparable to that of Bim^−/− mice, the increased numbers of pericytes were not to the extent noted in Bim^−/− mice. These changes were supported by partial protection of retinal vessels from hyperoxia in Bax^−/− mice compared to that noted in Bim^−/− mice. Thus, Bim-Bax driven pathway is sufficient to remove excess endothelial cells but not pericytes during postnatal retinal vascularization and hyperoxia-mediated vessel obliteration. Thus, additional Bim-mediated pathway(s) are required for removal of pericytes and hyperoxia-mediated vessel obliteration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110107"},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282671","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":"Controlled elevation of intraocular pressure in anesthetized mice","authors":"Diana C. Lozano,&nbsp;William O. Cepurna,&nbsp;Elaine C. Johnson,&nbsp;John C. Morrison","doi":"10.1016/j.exer.2024.110106","DOIUrl":"10.1016/j.exer.2024.110106","url":null,"abstract":"<div><div>Our purpose was to develop a protocol for prolonged anesthesia in mice and evaluate optic nerve axon injury in response to 4 h of controlled elevation of intraocular pressure (CEI). During CEI, C57BL/6 male mice (3–5 months old) were anesthetized with 1.5% isoflurane with 100% oxygen for 4 h and placed on a warm platform, with expired gas and anesthetic actively evacuated. Lactated ringers (0.5 ml) with 5% dextrose was administered subcutaneously at the start and end of CEI. Physiological parameters (oxygen saturation = O₂, heart rate = HR, systolic blood pressure = SBP, and temperature) were monitored throughout the 4-h CEI. One eye was cannulated with polyurethane tubing connected to a balanced salt solution reservoir and IOP elevated to 20 (N = 18), 30 (N = 13), 50 (N = 14), and 60 mmHg (N = 16). An additional group of 22 female mice was exposed to CEI of 60 mmHg. Fourteen days after CEI, optic nerves were assessed for axonal injury by masked observers that assigned a grade on a scale from 1 (normal) to 5 (&gt;50% of axons degenerating). CEI optic nerve injury was compared to injury assessed in contralateral optic nerves (N = 84) and naïve optic nerves (N = 18) using a one-way ANOVA followed by Kruskal-Wallis test for multiple comparisons. The relationship between optic nerve injury, physiological parameters, and IOP were assessed by linear regression analyses. Physiologic parameters remained stable throughout CEI (O₂ = 95 ± 9%; HR = 450 ± 39; SBP = 102 ± 15 mmHg, and temperature = 38 ± 0.7 °C) and were not statistically different between groups (all comparisons had P &gt; 0.5). Mean optic nerve injury grades (±SD) for naïve optic nerves (1.01 ± 0.02) were not significantly different from fellow/contralateral optic nerves (1.03 ± 0.07, P &gt; 0.99), or from CEI of 20 mmHg (1.04 ± 0.08, P &gt; 0.99) or 30 mmHg (1.05 ± 0.06, P = 0.6). However, animals exposed to CEI of 50 mmHg (2.09 ± 1.43, P = 0.0005) and 60 mmHg (male: 2.86 ± 1.30, P &lt; 0.0001, female: 1.63 ± 1.00, P = 0.0006) developed significant optic nerve injury relative to their fellow/contralateral optic nerves. Axonal injury grades following a CEI of 60 mmHg were not significantly different between male and female mice (P = 0.19). Optic nerve injury positively correlated (P &lt; 0.0001) with IOP and not with physiological parameters, indicating that the optic nerve injury is IOP-related. In conclusion, prolonged anesthesia in mice requires careful attention to animal physiology. With this, a 4-h exposure to elevated IOP can produce significant optic nerve injury with IOPs equal to or greater than 50 mmHg. We provide detailed descriptions of methods and materials for producing prolonged elevations of IOP in mice while maintaining and monitoring their physiology, as well as a unique, cost-effective transducer system for monitoring pressure delivery.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110106"},"PeriodicalIF":3.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282672","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":"Increased susceptibility of human limbal aniridia fibroblasts to oxidative stress","authors":"Simon Trusen ,&nbsp;Julia Sarah Alexandra Zimmermann ,&nbsp;Fabian Norbert Fries ,&nbsp;Zhen Li ,&nbsp;Ning Chai ,&nbsp;Berthold Seitz ,&nbsp;Shweta Suiwal ,&nbsp;Maryam Amini ,&nbsp;Nóra Szentmáry ,&nbsp;Tanja Stachon","doi":"10.1016/j.exer.2024.110105","DOIUrl":"10.1016/j.exer.2024.110105","url":null,"abstract":"<div><div>Aniridia-associated keratopathy originates from a haploinsufficiency of the transcription factor PAX6 (PAX6^+/−). In the corneal epithelium of PAX6^+/− mice, a significant increase in oxidized proteins was observed, accompanied by impaired compensation for elevated oxidative stress (OS). The extent to which limbal fibroblast cells (LFCs) are affected by an increased susceptibility to OS in cases of congenital aniridia (AN) has not been determined, yet. Our aim was to examine the impact of OS on antioxidant enzyme expression in normal and AN-LFCs. Following isolation and culture of primary LFCs (n = 8) and AN-LFCs (n = 8), cells were treated with cobalt chloride for 48 h to chemically induce hypoxic conditions and OS. Subsequently, HIF-1α/-2α, PHD1/2, Nrf2, CAT, SOD1, PRDX6, and GPX1 gene expression was examined by qPCR. SOD1, PRDX6, and GPX1 protein levels were assessed from the cell lysate by Western blot. The induction of hypoxia led to reduced HIF-1α gene expression in both fibroblast groups (<em>p</em><em>≤</em> <em>0.</em>008), while the decrease in PHD1 was limited to AN-LFCs (<em>p</em> = 0.0007). On the other hand, under hypoxic conditions, PHD2 showed higher mRNA expression in AN-LFCs compared to normal LFCs (<em>p</em> = 0.013). As a result of OS, the mRNA levels of Nrf2 (<em>p</em><em>&lt;</em>0.0001) and the antioxidant enzymes CAT (<em>p</em> = 0.005), SOD1 (<em>p</em> = 0.005), GPX1 (<em>p</em> = 0.002) decreased in AN-LFCs. This was accompanied by an increased protein expression of SOD1 (<em>p</em> = 0.019) and PRDX6 (<em>p</em><em>=</em>0.0009). In the normal LFC group, the induced extent of OS had no impact on the gene (<em>p</em><em>≥</em>0.151) and protein expression (<em>p</em> ≥ 0.629) of antioxidant enzymes, except for the GPX1 mRNA level (<em>p</em> = 0.027). AN-LFCs exhibit higher susceptibility to OS than normal LFCs. Therefore, in AN-LFCs, there are sustained alterations in gene and protein expression of antioxidative enzymes even after 48 h of CoCl₂ treatment.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110105"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282675","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":"Moringa oleifera hydroalcoholic leaf extracts mitigate valproate-induced oxidative status in the extraorbital lacrimal gland in a rat model","authors":"Burcin Alev-Tuzuner ,&nbsp;Sehkar Oktay ,&nbsp;Eda Cergel ,&nbsp;Gulsum Elik ,&nbsp;Umar Faruk Magaji ,&nbsp;Ozlem Sacan ,&nbsp;Refiye Yanardag ,&nbsp;Aysen Yarat","doi":"10.1016/j.exer.2024.110104","DOIUrl":"10.1016/j.exer.2024.110104","url":null,"abstract":"<div><div>Dysfunction of the extraorbital lacrimal gland (ELG) can lead to loss of vision due to damage to the epithelium of cornea. The broad-spectrum anti-epileptic drug sodium valproate (SV) has numerous side effects. <em>Moringa oleifera (M.oleifera)</em> is widely used as a food and in folk medicine. The effects of orally administered SV and <em>M. oleifera</em> hydroalcoholic leaf extract on rat ELG were investigated in this study by analysing both antioxidant and oxidant parameters. Additionally, boron level and tissue factor (TF) activity were determined. Protein changes were detected by sodium dodecyl sulfate gel electrophoresis (SDS-PAGE). Significantly lower values of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and total antioxidant status (TAS) were observed in the SV group compared to the control group. Treatment with Moringa extract significantly increased SOD, CAT and TAS values in the Moringa given SV group (SVM). While no significant differences were observed between the sialic acid values of the groups, lipid peroxidation (LPO), nitric oxide (NO) and total oxidant status (TOS) values were significantly elevated in the SV group compared to the control group. Due to the effect of Moringa extract, LPO, NO and TOS levels were significantly decreased in the SVM group compared to the SV group. TF activity was not meaningfully altered between groups. Compared to control rats, oxidative stress index (OSI) level significantly increased, whereas the boron level decreased in the SV group. Moringa extract treatment noticeably reduced OSI in the SVM group. According to SDS-PAGE, decreases in the density of protein bands with molecular weights of 51, 83, and 90 kDa were observed in SV given rats compared to the other groups. These decreases were reversed by the administration of Moringa extract. Moringa extract has shown protective properties arising from antioxidant potential, especially with its very low OSI value. Individuals undergoing SV treatment and having ELG complications might consider using Moringa extract to mitigate valproate induced damage.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110104"},"PeriodicalIF":3.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282676","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":"A comprehensive genotype-phenotype study in 203 individuals with retinoblastoma","authors":"Yoo Jin Lee ,&nbsp;Jeong Hun Kim ,&nbsp;Sang-Yeon Lee ,&nbsp;Dong Hyun Jo","doi":"10.1016/j.exer.2024.110102","DOIUrl":"10.1016/j.exer.2024.110102","url":null,"abstract":"<div><p>Retinoblastoma is the most common intraocular tumor in children and is caused by biallelic inactivation of the <em>RB1</em> gene. The identification of <em>RB1</em> germline variants in patients with retinoblastoma and their families is critical for early diagnosis and prevention. In this study, genetic testing was conducted on the genomic DNA of 203 patients with retinoblastoma using a combined approach of direct sequencing and multiplex ligation-dependent probe amplification (MLPA) assays for genotype-phenotype correlation studies. Sixty-five germline variants were identified in 80 of the 203 patients, with 67 bilateral and 13 unilateral retinoblastoma cases. The variant detection rates in the bilateral and unilateral cases were 88% and 10%, respectively. Eighteen novel variants were identified. Variants were classified according to their presence, mutation pattern, location, molecular consequences, and pathogenicity. Subsequently, the genotypes and phenotypes of the 203 patients were evaluated. Variants were associated with age at diagnosis (<em>p</em> &lt; 0.001), laterality (<em>p</em> &lt; 0.001), and tumor size (<em>p</em> = 0.010). The molecular consequences of the variants were related to laterality (<em>p</em> &lt; 0.001) and tumor size (<em>p</em> = 0.001). The pathogenicity of the variants was associated with age at diagnosis (<em>p</em> = 0.001), laterality (<em>p</em> = 0.0212), treatment response (<em>p</em> = 0.0470), and tumor size (<em>p</em> = 0.002). These results suggest that patient phenotypes are associated with the inherent characteristics of germline <em>RB1</em> variants. These findings indicate the potential application of genetic testing results in clinical practice.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110102"},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270643","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":"Comparative analysis of In vivo endothelial cell translatomes across central nervous system vascular beds","authors":"Ana J. Chucair-Elliott ,&nbsp;Kevin Pham ,&nbsp;Audrey C.A. Cleuren ,&nbsp;Christopher M. Schafer ,&nbsp;Courtney T. Griffin ,&nbsp;Sarah R. Ocanas ,&nbsp;Willard M. Freeman ,&nbsp;Michael H. Elliott","doi":"10.1016/j.exer.2024.110101","DOIUrl":"10.1016/j.exer.2024.110101","url":null,"abstract":"<div><p>Endothelial cells (ECs) display organ- and tissue-specific heterogeneity. In the eye, the retinal and choroidal vascular beds are distinct networks with different molecular and morphological properties that serve location-specific functions, i.e., the former maintaining a tight barrier and the latter, a permeable fenestrated vasculature. Given that retinal health critically relies on the function of these vascular beds and that their dysfunction is implicated in a variety of retinal diseases, a molecular understanding of both physiological and pathophysiological characteristics of these distinct vasculatures is critical. Given their interspersed anatomic distribution among parenchymal cells, the study of EC gene expression, <em>in vivo</em>, has been hampered by the challenge of isolating pure populations of ocular ECs in sufficient quantities for large-scale transcriptomics. To address this challenge, we present a methodological and analytical workflow to facilitate inter-tissue comparisons of the <em>in vivo</em> EC translatome isolated from choroid, retina, and brain using the Cre-inducible NuTRAP flox construct and two widely-used endothelial Cre mouse lines: constitutive Tie2-Cre and tamoxifen-inducible Cdh5-CreERT2. For each Cre line, inter-tissue comparison of TRAP-RNAseq enrichment (TRAP-isolated translatome vs input transcriptome) showed tissue-specific gene enrichments with differential pathway representation. For each mouse model, inter-tissue comparison of the EC translatome (choroid vs brain, choroid vs retina, and brain vs retina) showed over 50% overlap of differentially expressed genes (DEGs) between the three paired comparisons, with differential pathway representation for each tissue. Pathway analysis of DEGs in the Cdh5-NuTRAP vs Tie2-NuTRAP comparison for retina, choroid, and brain predicted inhibition of processes related to myeloid cell function and activation, consistent with more specific targeting of ECs in the Cdh5-NuTRAP than in the Tie2-NuTRAP model which also targets hematopoietic progenitors giving rise to immune cells. Indeed, while TRAP enriches for EC transcripts in both models, myeloid transcripts were also captured in the Tie2-NuTRAP model which was confirmed using cell sorting. We suggest experimental/analytical considerations should be taken when selecting Cre-lines to target ECs.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110101"},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014483524003233/pdfft?md5=e65d6a1b03aa1ed7f8ca3ab69fa4bbe9&pid=1-s2.0-S0014483524003233-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270645","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":"Estrogen, via ESR2 receptor, prevents oxidative stress-induced Müller cell death and stimulates FGF2 production independently of NRF2, attenuating retinal degeneration","authors":"Hiroshi Tawarayama ,&nbsp;Keiko Uchida ,&nbsp;Hirokazu Hasegawa ,&nbsp;Masaaki Yoshida ,&nbsp;Maki Inoue-Yanagimachi ,&nbsp;Wataru Sato ,&nbsp;Noriko Himori ,&nbsp;Masayuki Yamamoto ,&nbsp;Toru Nakazawa","doi":"10.1016/j.exer.2024.110103","DOIUrl":"10.1016/j.exer.2024.110103","url":null,"abstract":"<div><div>In this study, we aimed to investigate the effects of the deficient antioxidative gene, nuclear factor-erythroid 2-related factor 2 (<em>Nrf2</em>), on 17β-estradiol (E₂)-mediated oxidative stress response, with a specific focus on growth factor production and cell death in Müller cells and retinal tissue. Administration of hydrogen peroxide (H₂O₂) reduced the viability of Müller cells derived from <em>Nrf2</em> wild-type (WT) and knockout (KO) mice. However, this effect was more significant in the KO cells than in the WT cells. Pretreatment with E₂ inhibited H₂O₂-induced cell death in both <em>Nrf2</em> WT and KO Müller cell genotypes. Small interfering RNA-mediated gene silencing of estrogen receptor 2 (<em>Esr2</em>) attenuated the cell survival-promoting activity of E₂ in <em>Nrf2</em> KO Müller cells, while other identified estrogen receptors, <em>Esr1</em> or G protein-coupled estrogen receptor 1 (<em>Gper1</em>), had no effect. Western blotting revealed higher ESR2 expression levels in <em>Nrf2</em> KO cells than in WT Müller cells. Conditioned media from E₂-and H₂O₂-treated <em>Nrf2</em> WT or KO Müller cells enhanced the dissociated retinal cell viability compared with H₂O₂-treated cells. Both quantitative reverse-transcription polymerase chain reaction assay (qRT-PCR) and enzyme-linked immunosorbent assay exhibited a significant increase in fibroblast growth factor 2 (FGF2) expression levels in E₂-and H₂O₂-treated <em>Nrf2</em> WT and KO Müller cells compared to those in E₂-treated cells. <em>In vivo,</em> administration of N-methyl-N-nitrosourea (MNU) reduced the thickness and cell density of the outer nuclear layer (ONL) in <em>Nrf2</em> KO mice and enhanced the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the ONL. However, E₂ administration attenuated these defects in MNU-treated mice. Concomitant administration of MNU and E₂ enhanced FGF2 protein levels in retinal lysates of <em>Nrf2</em> KO mice. In conclusion, E₂ demonstrated a significant role in preventing oxidative stress-induced retinal cell death by stimulating FGF2 production in Müller cells, independent of the <em>Nrf2</em> gene. Based on these findings, we anticipate that exogenous administration of estrogens or ESR2-selective agonists could aid in treating patients with oxidative stress-related retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110103"},"PeriodicalIF":3.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282673","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 epithelial-stromal constructs to study differences associated with diabetes mellitus","authors":"Brenna S. Hefley ,&nbsp;Tina B. McKay ,&nbsp;Audrey E.K. Hutcheon ,&nbsp;Joseph B. Ciolino ,&nbsp;Dimitrios Karamichos","doi":"10.1016/j.exer.2024.110100","DOIUrl":"10.1016/j.exer.2024.110100","url":null,"abstract":"<div><p>Diabetes mellitus (DM) is a common metabolic disease associated with severe macrovascular and microvascular complications that influence nearly every tissue in the body, including the anterior and posterior segments of the eye. In the cornea, DM is associated with recurrent epithelial erosion and reduced wound-healing capacity, which increases the risk of corneal scarring. We previously developed a co-culture model of the cornea consisting of immortalized human corneal epithelial cells (hCE-TJ) overlaying a self-assembled stromal layer generated by human corneal fibroblasts (hCFs) over a 4-week period. In this study, we investigated epithelial-stromal constructs generated from hCFs derived from subjects with Type 1 (T1DM) or 2 diabetes (T2DM) compared to controls. We found that T2DM constructs exhibited a disrupted epithelium and a thicker, stratified stromal layer compared to controls or T1DM. Both T1DM and T2DM stromal constructs expressed lower expression of thrombospondin-1 in isolated extracellular vesicles (EVs) compared to controls with no significant difference observed in the presence of epithelial cells, suggesting that reduced provisional matrix secretion in the corneal stroma may be a factor that promotes delayed corneal wound healing in diabetes. The tetraspanins are established extracellular vesicle (EV) markers and include CD63, CD81, and CD9, and were highly expressed by EVs in all three cell types. Control corneal stromal fibroblasts produced more and larger EVs when compared to T1DM and T2DM hCF-derived EVs, supporting a role for altered cell-cell communication in the context of DM. Further characterization of EVs and their cargo is expected to aid in the development of targeted treatments to improve corneal wound healing.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110100"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270642","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":"Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy","authors":"Tianyi Zong ,&nbsp;Tong Mu ,&nbsp;Chengye Tan ,&nbsp;Tianhua Xie ,&nbsp;Miao Zhuang ,&nbsp;Yan Wang ,&nbsp;Ziwen Li ,&nbsp;Qian Yang ,&nbsp;Meili Wu ,&nbsp;Jiping Cai ,&nbsp;Xiaolu Wang ,&nbsp;Yong Yao","doi":"10.1016/j.exer.2024.110097","DOIUrl":"10.1016/j.exer.2024.110097","url":null,"abstract":"<div><p>Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-β2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-β2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and β-catenin in the PVR membranes. ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110097"},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270641","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":"Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes","authors":"Xiaona Liu,&nbsp;Lingling Yan,&nbsp;Junchao Wei,&nbsp;Ce Wu,&nbsp;Jie Zhang,&nbsp;Jie Song,&nbsp;Zhipeng Gao,&nbsp;Halima Ben Hilal,&nbsp;Xiaona Li,&nbsp;Weiyi Chen","doi":"10.1016/j.exer.2024.110095","DOIUrl":"10.1016/j.exer.2024.110095","url":null,"abstract":"<div><p>The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 μm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm² for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.</p></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110095"},"PeriodicalIF":3.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270640","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}