Substrate stiffness and pressure alter retinal Müller glia response and extracellular matrix production

Q3 Biochemistry, Genetics and Molecular Biology

Biomaterials and biosystems Pub Date : 2025-07-07 DOI:10.1016/j.bbiosy.2025.100114

Laura Prieto-López , Xandra Pereiro , Emilio J. González Ramírez , Noelia Ruzafa , Alicia Alonso , Kristian Franze , Elena Vecino

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Abstract

Background

The retina is highly influenced by its mechanical environment, with Müller glia (MG) acting as key mechanosensors and extracellular matrix (ECM) producers. This study examined MG responses to substrate stiffness and high pressure (HP), and whether TGF-β1 modulation could mitigate these effects.

Methods

Primary MG from adult rat retinas were cultured on glass (Young’s modulus E’=∼1 gigapascal (GPa)) and polyacrylamide gels (10 kPa and 100 kPa). MG were exposed to atmospheric and 70 mmHg (HP) conditions, with TGF-β1 pharmacologically blocked.

Results

On glass and 100 kPa gels, MG survival, cell area, and ECM deposition (collagen I, IV, and fibronectin) increased, with cells adopting a fusiform shape and more dedifferentiated state. Under HP, survival decreased on stiffer substrates, though cell area and morphology remained unchanged. HP increased ECM deposition, which was reduced by TGF-β1 inhibition.

Conclusions

Our findings suggest that MG response to mechanical stress alter their survival and cell area, and increases ECM secretion, highlighting TGF-β1 as a potential therapeutic target.

Abstract Image

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基质硬度和压力改变视网膜神经胶质反应和细胞外基质的产生

视网膜受其机械环境的高度影响，突触神经胶质（MG）是关键的机械传感器和细胞外基质（ECM）的产生者。本研究检测了MG对基质刚度和高压（HP）的响应，以及TGF-β1调节是否可以减轻这些影响。方法用玻璃（杨氏模量E′= ~ 1gigapascal (GPa)）和聚丙烯酰胺凝胶（10kpa和100kpa）培养成年大鼠视网膜原代MG。MG暴露于大气和70 mmHg （HP）条件下，TGF-β1被药物阻断。结果玻璃凝胶和100 kPa凝胶的MG存活率、细胞面积和ECM沉积（胶原I、IV、纤维连接蛋白）均增加，细胞呈梭状，呈去分化状态。HP作用下，在较硬的基质上存活率下降，但细胞面积和形态保持不变。HP增加了ECM沉积，而抑制TGF-β1则降低了ECM沉积。结论MG对机械应力的反应改变了它们的存活和细胞面积，增加了ECM的分泌，提示TGF-β1是潜在的治疗靶点。

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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