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Proteomic analysis of effects of 1% atropine in myopia therapy in Guinea pigs. 1%阿托品对豚鼠近视治疗效果的蛋白质组学分析。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-25 DOI: 10.1016/j.exer.2024.110224
Chen Chu, Luyao Ye, Qingqing Chi, Jiangnan He, Jianfeng Zhu

Myopia is a significant global public health issue. Key interventions for managing myopia include atropine treatment, optical correction, and surgical methods. This study focused on evaluating alterations in retinal protein expression after atropine therapy for myopia. Guinea pigs were randomly divided into four groups: control (CON), monocular form-deprivation myopia (FDM), FDM with 2-week atropine treatment (FDM + ATR), and atropine-only treatment (ATR). After two weeks of FDM induction, the FDM group showed significant differences in refractive error and increased axial lengths. In comparing the retinas of myopic and normal eyes, 30 proteins were found to have increased expression, while 8 proteins showed decreased expression. Atropine-treated retinas exhibited 73 proteins with increased expression and 29 proteins with decreased expression compared to the normal eyes. A total of 11 regulated proteins overlapped between the FDM + ATR vs FDM and FDM vs CON groups. IPA analysis indicates significant alterations in amino acid metabolism, energy production, post-translational modification, small molecule biochemistry, and free radical scavenging. Our study identifies retinal protein changes in myopic guinea pigs and in guinea pigs treated with atropine after myopia. These proteins could serve as potential targets for atropine treatment of myopia.

近视是一个重大的全球公共卫生问题。管理近视的主要干预措施包括阿托品治疗、光学矫正和手术方法。本研究的重点是评估阿托品治疗近视后视网膜蛋白表达的改变。将豚鼠随机分为4组:对照组(CON)、单眼形态剥夺性近视组(FDM)、单眼形态剥夺性近视组(FDM + ATR)和单眼形态剥夺性近视组(ATR)。FDM诱导两周后,FDM组在屈光不正和增加的眼轴长度方面表现出显著差异。比较近视眼和正常眼视网膜,发现30个蛋白表达增加,8个蛋白表达减少。与正常眼睛相比,阿托品处理的视网膜有73种蛋白表达增加,29种蛋白表达减少。FDM + ATR组与FDM组和FDM组与CON组之间共有11个受调节蛋白重叠。IPA分析表明氨基酸代谢、能量产生、翻译后修饰、小分子生物化学和自由基清除能力发生了显著变化。我们的研究确定了近视豚鼠和近视后接受阿托品治疗的豚鼠视网膜蛋白的变化。这些蛋白可作为阿托品治疗近视的潜在靶点。
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引用次数: 0
Exploring ocular disorders in Parkinson's disease: A comprehensive review and future perspectives. 帕金森氏病眼部疾病的研究:综述与展望
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-24 DOI: 10.1016/j.exer.2024.110225
Minal Thacker, Ka Ying Wong, Liping Zhou, Juewen Liu, Man-Sau Wong

Parkinson's disease (PD) is a multifaceted neurodegenerative disorder characterized by predominantly motor symptoms. However, recent research has broadened our understanding of PD by revealing its impact on non-motor functions, including ocular manifestations. This review explored the intricate relationship between PD and ocular health, shedding light on the mechanisms underlying common ocular diseases such as dry eye disease, cataract, glaucoma, age-related macular degeneration, and diabetic retinopathy. It also underscores the importance of recognizing ocular manifestations as potential early markers of PD, as well as their impact on patients' daily activities, necessitating prompt identification and intervention to prevent complications and enhance the overall quality of life. Furthermore, future research should prioritize unraveling the potential association between PD and other prevalent ocular diseases, such as myopia, to formulate effective treatment strategies.

帕金森病(PD)是一种以运动症状为主的多方面神经退行性疾病。然而,最近的研究通过揭示PD对包括眼部表现在内的非运动功能的影响,拓宽了我们对PD的理解。本文探讨了PD与眼部健康之间的复杂关系,揭示了干眼病、白内障、青光眼、年龄相关性黄斑变性和糖尿病视网膜病变等常见眼部疾病的发病机制。它还强调了将眼部表现视为PD的潜在早期标志的重要性,以及它们对患者日常活动的影响,需要及时识别和干预,以预防并发症并提高整体生活质量。此外,未来的研究应优先揭示PD与其他常见眼部疾病(如近视)之间的潜在关联,以制定有效的治疗策略。
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引用次数: 0
Photobiomodulation inhibits retinal degeneration in diabetic mice through modulation of stem cell mobilization and gene expression. 光生物调节通过调节干细胞动员和基因表达抑制糖尿病小鼠视网膜变性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-22 DOI: 10.1016/j.exer.2024.110218
Jingyan Ge, Yinan Zhang, Ling Han, Liangliang Zhao, Hongwei Zhao, Dan Qiao, Yan Cheng

The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM + PBM group received LED illumination (wavelength 670 nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α in retina, the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of E-Cadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4 min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.

2型糖尿病(DM2)患者的数量正在增加,其中超过30%的DM2患者将发展为糖尿病视网膜病变(DR)。DR的现有治疗方法有其局限性。寻找其他有效的替代治疗方法具有重要意义。本研究旨在探讨光生物调节(PBM)对糖尿病视网膜病变的有益作用及其机制。采用链脲佐菌素建立雄性小鼠糖尿病模型。糖尿病组(DM)小鼠不进行任何治疗,DM+PBM组小鼠接受LED照明(波长670nm),每天1次,连续20周。检测大鼠视网膜血管变性变化,视网膜E-Cadherin、N-Cadherin表达水平及c-kit、CXCR4、MYPT1、SCF、SDF1-α mRNA水平,外周血SDF-1α、SCF水平及表达c-kit、SCF -1的LSK细胞数量。PBM能显著抑制糖尿病视网膜血管的退行性改变,降低E-Cadherin、N-Cadherin的表达水平以及c-kit、CXCR4、MYPT1、SCF、SDF1-α mRNA水平,升高VEGF mRNA水平。PBM还能增加糖尿病小鼠外周血中SDF-1α和SCF的水平以及表达c-kit和sca-1的LSK细胞的数量。连续20周,4分钟/天的PBM显著抑制糖尿病视网膜血管的退行性改变,PBM可能是通过促进骨髓干细胞向循环和糖尿病视网膜组织的迁移来产生其对视网膜的有益作用。本研究为糖尿病视网膜病变的治疗提供了新的治疗方向和实验基础。
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引用次数: 0
How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration. 线粒体、溶酶体和其他细胞器之间的相互作用如何预防或促进干性老年性黄斑变性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-22 DOI: 10.1016/j.exer.2024.110219
Aparna Lakkaraju, Patricia Boya, Marie Csete, Deborah A Ferrington, James B Hurley, Alfredo A Sadun, Peng Shang, Ruchi Sharma, Debasish Sinha, Marius Ueffing, Susan E Brockerhoff

Organelles such as mitochondria, lysosomes, peroxisomes, and the endoplasmic reticulum form highly dynamic cellular networks and exchange information through sites of physical contact. While each organelle performs unique functions, this inter-organelle crosstalk helps maintain cell homeostasis. Age-related macular degeneration (AMD) is a devastating blinding disease strongly associated with mitochondrial dysfunction, oxidative stress, and decreased clearance of cellular debris in the retinal pigment epithelium (RPE). However, how these occur, and how they relate to organelle function both with the RPE and potentially the photoreceptors are fundamental, unresolved questions in AMD biology. Here, we report the discussions of the "Mitochondria, Lysosomes, and other Organelle Interactions" task group of the 2024 Ryan Initiative for Macular Research (RIMR). Our group focused on understanding the interplay between cellular organelles in maintaining homeostasis in the RPE and photoreceptors, how this could be derailed to promote AMD, and identifying where these pathways could potentially be targeted therapeutically.

细胞器如线粒体、溶酶体、过氧化物酶体和内质网形成高度动态的细胞网络,并通过物理接触部位交换信息。虽然每个细胞器都有独特的功能,但这种细胞器间的相互作用有助于维持细胞的稳态。年龄相关性黄斑变性(AMD)是一种毁灭性致盲疾病,与线粒体功能障碍、氧化应激和视网膜色素上皮(RPE)细胞碎片清除减少密切相关。然而,这些是如何发生的,以及它们如何与RPE和潜在的光感受器的细胞器功能相关,是AMD生物学中根本的,未解决的问题。在这里,我们报告了2024年瑞安黄斑研究倡议(RIMR)的“线粒体,溶酶体和其他细胞器相互作用”任务组的讨论。我们的研究小组专注于了解细胞器在维持RPE和光感受器内稳态方面的相互作用,这是如何促进AMD的,并确定这些途径在哪里可能成为治疗的靶点。
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引用次数: 0
The vectors went in two-by-two: Transduction efficiency and tolerability of dual and triple rAAV vector delivery following intravitreal injection for genome-editing applications. 载体分为两部分:在基因组编辑应用的玻璃体内注射后,双重和三重rAAV载体传递的转导效率和耐受性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110223
Rachel L Fehrman, Kristina J Chern, Kyle P Stoltz, Daniel M Lipinski

Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. In vivo delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.1kb) it is unfortunately usually necessary to split therapeutic transgene cassettes across multiple co-administered vector genomes. While the efficiency with which multiple vector genomes recombine following cellular entry has been studied extensively, another potentially limiting factor is the likelihood of target cells (e.g. retinal ganglion cells) receiving two or more vectors containing genomes that correspond to the full-length expression cassette when recombined. In this study we examine the efficiency with which two or more vector genomes transduce various retinal cell types following intravitreal administration. rAAV2/2[MAX] vectors expressing individual fluorescent reporters (GFP, BFP or mCherry) were co-injected intravitreally singly or in combination (dual or triple), allowing the extent of co-transduction to be assessed through multimodal in vivo imaging, electroretinography, flow cytometry and post-mortem histology. We find that intravitreal co-administration of vectors containing multiple genomes is well tolerated - with no observed alterations in retinal thickness or ERG amplitudes - but that co-transduction efficiency decreases significantly with increasing genome number. As such co-transduction of multiple vectors may be a major bottleneck limiting gene editing of inherited disorders affecting the inner retina.

基因组或引体编辑已成为治疗影响内视网膜的遗传性疾病(如显性视神经病变)的一种很有前途的工具。基因编辑器(如Cas9)的体内递送通常使用重组腺相关病毒(rAAV)载体来实现,这种载体具有广泛的细胞趋向性,并且在玻璃体内给药后耐受性良好。由于基因编辑构建体的体积较大,rAAV (
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引用次数: 0
Protective effects of different exercise modalities on oxidative stress in animal models of high intraocular pressure and diabetes. 不同运动方式对高眼压和糖尿病动物模型氧化应激的保护作用。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110216
Sabrina Nau da Silva Piazza, Paula Bortoluzzi Canteiro, Natalia Dos Santos Tramontin, Giulia Strapazzon, Vanessa de Moraes Andrade, Alexandre Pastoris Muller

High intraocular pressure (HIOP) and high glucose levels are associated with oxidative stress. Although physical exercise protects against oxidative damage, its specific impact on eye health remains unclear. Thus, this study aimed to assess the impact of physical exercise on the oxidative status of whole eyes in male Swiss mice subjected to HIOP model and cafeteria diet (CD). In experiment one, mice were divided into sedentary, aerobic, and strength (four-week physical exercise) groups and subjected to an HIOP/ischemia model. In experiment two, mice were submitted to CD and voluntary physical exercise for 18 weeks, according to the following groups: sedentary control, sedentary CD, exercise control, and exercise CD. Experiment one revealed elevated 2',7'-dichlorodihydrofluorescein (DCFH) levels in aerobic group, which decreased in all groups after ischemia. Nitrite levels were decreased on strength than in sedentary group. The superoxide dismutase (SOD) activity did not change in all treatments. Although catalase (CAT) activity increased in aerobic and strength groups, and after ischemia in all groups. In experiment two, the sedentary CD group presented higher body weight than the other groups. DCFH levels were increased in the exercise control and reduced in the exercise CD compared with the other groups. CAT activity and sulfhydryl groups were decreased, while protein carbonylation was increased in the sedentary CD group compared with the other groups. Thus, these results suggested that physical exercise promoted antioxidant effects on eyes exposed to an HIOP model and CD.

高眼压(HIOP)和高血糖水平与氧化应激有关。虽然体育锻炼可以防止氧化损伤,但它对眼睛健康的具体影响尚不清楚。因此,本研究旨在评估体育锻炼对HIOP模型和自助饮食(CD)雄性瑞士小鼠全眼氧化状态的影响。实验一,将小鼠分为久坐组、有氧组和力量组(4周体育锻炼),建立HIOP/缺血模型。实验二,小鼠连续18周进行CD和自愿体育锻炼,分为久坐对照组、久坐CD组、运动对照组和运动CD组。实验一显示有氧组小鼠2’,7’-二氯二氢荧光素(DCFH)水平升高,缺血后各组小鼠DCFH水平均下降。与久坐组相比,体力组亚硝酸盐水平降低。超氧化物歧化酶(SOD)活性在各处理中均无明显变化。虽然过氧化氢酶(CAT)活性在有氧组和力量组以及缺血后均有所增加。在实验二中,久坐的乳糜泻组的体重高于其他组。与其他组相比,运动对照组的DCFH水平升高,运动CD组的DCFH水平降低。与其他组相比,久坐CD组的CAT活性和巯基降低,而蛋白质羰基化增加。因此,这些结果表明,体育锻炼促进了暴露于HIOP模型和CD的眼睛的抗氧化作用。
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引用次数: 0
Effect of the IL-6 trans-signaling pathway in the absence or presence of TGF-β2 on Schlemm's canal endothelial cells. TGF-β2缺失或存在时IL-6反式信号通路对施莱姆管内皮细胞的影响
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110215
Mai Urahashi, Tomokazu Fujimoto, Miyuki Inoue-Mochita, Toshihiro Inoue

Intraocular pressure (IOP) is regulated through the balance of production and drainage of aqueous humor. The main route of aqueous-humor outflow comprises the trabecular meshwork (TM) and Schlemm's canal (SC). We reported that IL-6 trans-signaling can inhibit TGF-β signaling in TM cells and may affect regulation of IOP. However, the function of IL-6 trans-signaling in SC cells remains unclear. Therefore, we investigated the role of IL-6 trans-signaling in monkey SC cells. Simultaneous treatment with IL-6 and soluble IL-6 receptor (sIL-6R) significantly decreased the trans-endothelial electrical resistance (TER) of SC cells and reduced aqueous-humor outflow resistance. Moreover, activation of IL-6 trans-signaling significantly reduced expression of fibronectin, ZO-1 and claudin-5, and increased that of several matrix metalloproteinases. We also investigated the effect of IL-6 trans-signaling on TGF-β2-induced changes in SC cells. Simultaneous treatment with IL-6 and sIL-6R significantly suppressed the TGF-β2-induced increase in the TER of SC cells but did not affect the activity of the TGF-β2 signaling pathway. By contrast, the TGF-β2-induced increases in the expression of fibronectin and collagen type I were significantly decreased upon simultaneous treatment with IL-6 and sIL-6R. The results show that IL-6 trans-signaling suppressed TGF-β2-induced increase in outflow resistance.

眼内压(IOP)是通过房水生成和排出的平衡来调节的。房水的主要流出途径包括小梁网(TM)和施莱姆管(SC)。我们报道了IL-6反式信号传导可以抑制TM细胞中TGF-β信号传导,并可能影响IOP的调节。然而,IL-6反式信号在SC细胞中的功能尚不清楚。因此,我们研究了IL-6反式信号在猴SC细胞中的作用。同时使用IL-6和可溶性IL-6受体(sIL-6R)可显著降低SC细胞的跨内皮电阻(TER)和房水流出阻力。此外,IL-6反式信号的激活显著降低了纤维连接蛋白、ZO-1和cladin -5的表达,并增加了几种基质金属蛋白酶的表达。我们还研究了IL-6反式信号通路对TGF-β2诱导的SC细胞变化的影响。IL-6和sIL-6R同时处理可显著抑制TGF-β2诱导的SC细胞TER升高,但不影响TGF-β2信号通路的活性。而IL-6和sIL-6R同时治疗时,TGF-β2诱导的纤维连接蛋白和I型胶原表达的升高明显降低。结果表明,IL-6反式信号通路抑制TGF-β2诱导的流出阻力增加。
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引用次数: 0
SP1/COL1A2/ZEB1 axis promotes TGF-β2-induced lens epithelial cell proliferation, migration, invasion and EMT process. SP1/COL1A2/ZEB1轴促进TGF-β2诱导的晶状体上皮细胞增殖、迁移、侵袭和EMT过程。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110220
Lili Zhao, Ping Wang, Lianyi Sun, Weimei Ma, Lei Yu

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. In this study, we used transforming growth factor beta-2 (TGF-β2)-induced SRA01/04 cells to mimic PCO cell model and explored the functions and underlying mechanisms of specific protein 1 (SP1) in TGF-β2-induced SRA01/04 cell development. MTT assay and EdU assay were carried out to explore the proliferation of SRA01/04 cells. Transwell assay and wound-healing assay were performed to investigate SRA01/04 cell migration and invasion. Chromatin Immunoprecipitation (ChIP) assay, dual-luciferase reporter assay and Co-immunoprecipitation (Co-IP) assay were used to analyze the relations of SP1, COL1A2 and ZEB1. TGF-β2 treatment led to the promotion of SRA01/04 cell proliferation, migration, invasion and EMT process. COL1A2 level was induced by TGF-β2 treatment and COL1A2 knockdown inhibited TGF-β2-induced SRA01/04 cell proliferation, migration, invasion and EMT. SP1 could activate the transcription of COL1A2. SP1 overexpression promoted TGF-β2-induced SRA01/04 cell injury by regulating COL1A2 expression. Moreover, COL1A2 interacted with ZEB1 and COL1A2 knockdown-mediated effects on the proliferation, migration, invasion and EMT of TGF-β2-induced SRA01/04 cells were abrogated by elevating ZEB1. SP1 regulated COL1A2 and then mediated ZEB1 to affect the proliferation, migration, invasion and EMT of TGF-β2-induced SRA01/04 cells.

后囊膜混浊是白内障术后最常见的并发症。本研究采用转化生长因子β -2 (TGF-β2)诱导的SRA01/04细胞模拟PCO细胞模型,探讨特异性蛋白1 (SP1)在TGF-β2诱导的SRA01/04细胞发育中的作用及其机制。采用MTT法和EdU法观察SRA01/04细胞的增殖情况。Transwell法和创面愈合法观察SRA01/04细胞的迁移和侵袭。采用染色质免疫沉淀(ChIP)法、双荧光素酶报告基因法和共免疫沉淀(Co-IP)法分析SP1、COL1A2与ZEB1的关系。TGF-β2处理可促进SRA01/04细胞增殖、迁移、侵袭和EMT过程。TGF-β2处理可诱导COL1A2水平,COL1A2敲低可抑制TGF-β2诱导的SRA01/04细胞增殖、迁移、侵袭和EMT。SP1可以激活COL1A2的转录水平。SP1过表达通过调节COL1A2表达促进TGF-β2诱导的SRA01/04细胞损伤。此外,COL1A2与ZEB1相互作用,COL1A2敲低介导的对TGF-β2诱导的SRA01/04细胞增殖、迁移、侵袭和EMT的影响通过上调ZEB1而被消除。SP1通过调控COL1A2,进而介导ZEB1影响TGF-β2诱导的SRA01/04细胞的增殖、迁移、侵袭和EMT。
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引用次数: 0
Taurine mechanism in preventing retinal cell damage from acute ocular hypertension through GTPBP3 regulation. 牛磺酸通过调节GTPBP3预防急性高眼压视网膜细胞损伤的机制。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110222
Wei Lu, Yuting Yang, Shunxiang Gao, Jihong Wu, Xinghuai Sun

We aimed to explore the protective effects and underlying mechanisms of taurine on retinal cells during acute ocular hypertension (AOH)-induced damage. Retinal morphology, apoptosis, mitochondrial structure, electroretinography, expression of GTP binding protein 3 (GTPBP3), and molecules in the unfolded protein response (UPR) were examined in an AOH mouse model and wild-type (WT) mice with or without intravitreal injection of taurine. For in vitro experiments, the GTPBP3 expression and endoplasmic reticulum (ER) stress were examined in R28 cell line under hydrogen peroxide (H2O2)-induced damage or hypoxia/reoxygenation (H/R)-induced damage, with or without taurine pretreatment. Taurine pretreatment alleviated retinal damage caused by AOH modeling. The GTPBP3 expression level decreased after AOH injury, and taurine pretreatment reversed this reduction. Retinas with decreased GTPBP3 expression showed reduced retinal ganglion cell (RGC) function, which could be reversed by intravitreal taurine injection. In H2O2-, H/R-, and AOH-induced damage, UPR were activated and alleviated by taurine pretreatment. GTPBP3 knockdown in R28 cells also activated the UPR, which was alleviated by taurine. A UPR activator downregulated GTPBP3 levels in normal R28 cells, whereas a UPR inhibitor upregulated GTPBP3 levels in GTPBP3 knockdown R28 cells. In conclusion, this study provides important evidence that taurine prevents retinal cell damage in mice exposed to AOH and modulates GTPBP3 expression via the UPR pathway. Interventions targeting this mechanism can be used as potential therapeutic targets for AOH damage.

本研究旨在探讨急性高眼压(AOH)损伤时牛磺酸对视网膜细胞的保护作用及其机制。在AOH小鼠模型和野生型(WT)小鼠(玻璃体内注射或不注射牛磺酸)中检测视网膜形态学、凋亡、线粒体结构、视网膜电图、GTP结合蛋白3 (GTPBP3)的表达以及未折叠蛋白反应(UPR)分子。在体外实验中,研究了过氧化氢(H2O2)诱导的损伤和缺氧/再氧化(H/R)诱导的损伤对R28细胞系GTPBP3表达和内质网(ER)应激的影响。牛磺酸预处理可减轻AOH模型造成的视网膜损伤。AOH损伤后GTPBP3表达水平下降,牛磺酸预处理逆转了这种下降。GTPBP3表达降低的视网膜显示视网膜神经节细胞(RGC)功能降低,玻璃体内注射牛磺酸可逆转这一现象。在H2O2-、H/R-和aoh诱导的损伤中,牛磺酸预处理可激活和减轻UPR。R28细胞中GTPBP3的下调也激活了UPR,牛磺酸可以减轻UPR的激活。UPR激活剂在正常R28细胞中下调GTPBP3水平,而UPR抑制剂在GTPBP3敲除的R28细胞中上调GTPBP3水平。总之,本研究提供了重要证据,证明牛磺酸可预防AOH暴露小鼠视网膜细胞损伤,并通过UPR通路调节GTPBP3的表达。针对这一机制的干预措施可以作为AOH损伤的潜在治疗靶点。
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引用次数: 0
Testosterone promotes photoreceptor degeneration in the sodium iodate model. 在碘酸钠模型中,睾酮促进光感受器变性。
IF 3 2区 医学 Q1 OPHTHALMOLOGY Pub Date : 2024-12-20 DOI: 10.1016/j.exer.2024.110221
Timothy T Lee, Brent A Bell, Ying Song, Joshua L Dunaief

Previously, we found that retinas of young male mice were more damaged than those of young female mice in the sodium iodate (NaIO3) model. The purpose of this study was to test whether reducing testosterone levels would be retina-protective. Male C57Bl/6J mice underwent surgical castration or sham surgery, then were given an intraperitoneal injection of NaIO3 at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Surgical castration partially protected photoreceptors, which was indicated by less photoreceptor layer thinning exhibited in OCT images compared to the sham surgery group. Consistent with this, qRT-PCR of castration group neural retinas revealed less reduction of rhodopsin mRNAs, and less upregulation of antioxidant as well as glucose transporter 1 mRNAs. ERG results also demonstrated partial preservation of both cone and rod function. These results indicate that surgical castration provided structural and functional protection to photoreceptors against NaIO3. These neuroprotective effects suggest that testosterone may be harmful to the stressed retina. Further investigation of this pathway could lead to a better understanding of the mechanisms involved in retinal degeneration.

在此之前,我们发现在碘酸钠(NaIO3)模型中,年轻雄性小鼠的视网膜损伤比年轻雌性小鼠更严重。这项研究的目的是测试降低睾丸激素水平是否对视网膜有保护作用。雄性C57Bl/6J小鼠经手术阉割或假手术后,腹腔注射25 mg/kg的NaIO3。一周后使用光学相干断层扫描(OCT)对小鼠进行成像。使用带有定制宏的ImageJ测量OCT图像中的视网膜厚度。注射后1周采用视网膜电图(ERG)检测视网膜功能。安乐死后,进行实时荧光定量PCR (qRT-PCR)。手术阉割部分保护了光感受器,与假手术组相比,OCT图像显示的光感受器层变薄较少。与此一致的是,去势组神经视网膜的qRT-PCR显示,视紫红质mrna的减少较少,抗氧化和葡萄糖转运蛋白1 mrna的上调较少。ERG结果也显示了锥和杆状体功能的部分保存。这些结果表明,手术去势对光感受器抗NaIO3具有结构和功能上的保护作用。这些神经保护作用表明睾酮可能对应激视网膜有害。对这一途径的进一步研究可以更好地理解视网膜变性的机制。
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Experimental eye research
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