Early ultrastructural damage in retina and optic nerve following intraocular pressure elevation

IF 1.5 4区心理学 Q4 NEUROSCIENCES

Vision Research Pub Date : 2025-02-01 DOI:10.1016/j.visres.2025.108544

Carla Andreia Abreu , Gabriel Ferraz , Rômulo C. dos Santos , Luciana Conde , Danillo P. Dantas , Bráulio S. Archanjo , Rafael Linden , Pedro M. Pimentel-Coelho , Silvana Allodi

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引用次数: 0

Abstract

Elevated intraocular pressure (IOP) is a significant risk factor for glaucoma, causing structural and functional damage to the eye. Increased IOP compromises the metabolic and structural integrity of retinal ganglion cell (RGC) axons, leading to progressive degeneration and influencing the ocular immune response. This study investigated early cellular and molecular changes in the retina and optic nerve (ON) following ocular hypertension (OHT). A pigmented rat model was used, with OHT induced through low-temperature cauterization of the limbal vascular plexus. To assess the effects at early time points after OHT, transmission electron microscopy (TEM) was employed to analyze ultrastructural changes in the retina and ON, while immunofluorescence was used to evaluate cellular responses. Flow cytometry was used to examine alterations in immune-cell populations. Within 24 h post-OHT, ultrastructural changes were detected in the cytoplasm of RGCs, indicating early cellular alterations undetectable by conventional microscopy. These ultrastructural modifications progressed further at 48 and 72 h, despite the absence of overt RGC loss or disruptions in retinal layer integrity. Changes in the axons and nodes of Ranvier were evident within the first 24 h after ocular hypertension, becoming more pronounced by 72 h. These findings offer novel insights into the early pathogenesis of glaucoma, highlighting critical early impacts that could guide the development of new therapeutic strategies to prevent irreversible RGC loss.

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眼压升高后视网膜和视神经早期超微结构损伤。

眼压升高是青光眼的重要危险因素，可引起眼睛的结构和功能损伤。IOP升高损害视网膜神经节细胞（RGC）轴突的代谢和结构完整性，导致进行性变性并影响眼部免疫反应。本研究探讨了高眼压（OHT）后视网膜和视神经（ON）的早期细胞和分子变化。采用大鼠色素模型，通过低温烧灼角膜缘血管丛诱导OHT。为了评估OHT后早期时间点的效果，透射电子显微镜（TEM）分析视网膜和ON的超微结构变化，免疫荧光法评估细胞反应。流式细胞术用于检测免疫细胞群的变化。在oht后24小时内，RGCs细胞质中检测到超微结构变化，表明常规显微镜无法检测到早期细胞改变。尽管没有明显的RGC丢失或视网膜层完整性破坏，但这些超微结构改变在48和72 h时进一步发展。在高眼压后的最初24小时内，Ranvier轴突和淋巴结的变化是明显的，在72小时内变得更加明显。这些发现为青光眼的早期发病机制提供了新的见解，突出了关键的早期影响，可以指导开发新的治疗策略，以防止不可逆的RGC损失。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Vision Research 医学-神经科学

CiteScore

3.70

自引率

16.70%

发文量

111

审稿时长

66 days

期刊介绍： Vision Research is a journal devoted to the functional aspects of human, vertebrate and invertebrate vision and publishes experimental and observational studies, reviews, and theoretical and computational analyses. Vision Research also publishes clinical studies relevant to normal visual function and basic research relevant to visual dysfunction or its clinical investigation. Functional aspects of vision is interpreted broadly, ranging from molecular and cellular function to perception and behavior. Detailed descriptions are encouraged but enough introductory background should be included for non-specialists. Theoretical and computational papers should give a sense of order to the facts or point to new verifiable observations. Papers dealing with questions in the history of vision science should stress the development of ideas in the field.