Pereiro Xandra, Ruzafa Noelia, Azkargorta Mikel, Elortza Félix, Acera Arantxa, Ambrósio António Francisco, Santiago Ana Raquel, Vecino Elena
Experimental Ophthalmo-Biology Group, Department of Cell Biology and Histology, University of the Basque Country UPV/EHU, 48940, Leioa, Spain.
Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal.
Cell Biosci. 2024 Jan 5;14(1):5. doi: 10.1186/s13578-023-01186-1.
Glaucoma, a progressive neurodegenerative disease, is a leading cause of irreversible vision loss worldwide. This study aims to elucidate the critical role of Müller glia (MG) in the context of retinal ganglion cell (RGC) death, particularly focusing on the influence of peripheral MG sensitivity to high pressure (HP).
Co-cultures of porcine RGCs with MG were isolated from both the central and peripheral regions of pig retinas and subjected to both normal and HP conditions. Mass spectrometry analysis of the MG-conditioned medium was conducted to identify the proteins released by MG under all conditions.
Peripheral MG were found to secrete a higher quantity of neuroprotective factors, effectively promoting RGC survival under normal physiological conditions. However, under HP conditions, co-cultures with peripheral MG exhibited impaired RGC survival. Moreover, under HP conditions, peripheral MG significantly upregulated the secretion of proteins associated with apoptosis, oxidative stress, and inflammation.
This study provides robust evidence suggesting the involvement of MG in RGC death in glaucoma, thus paving the way for future therapeutic investigations.
青光眼是一种进行性神经退行性疾病,是全球不可逆视力丧失的主要原因。本研究旨在阐明米勒胶质细胞(MG)在视网膜神经节细胞(RGC)死亡过程中的关键作用,尤其关注外周MG对高压(HP)的敏感性影响。
从猪视网膜的中央和外周区域分离出猪RGC与MG的共培养物,并使其处于正常和高压条件下。对MG条件培养基进行质谱分析,以鉴定MG在所有条件下释放的蛋白质。
发现外周MG分泌更高量的神经保护因子,在正常生理条件下有效促进RGC存活。然而,在高压条件下,与外周MG的共培养物中RGC存活受损。此外,在高压条件下,外周MG显著上调与细胞凋亡、氧化应激和炎症相关的蛋白质分泌。
本研究提供了有力证据,表明MG参与青光眼患者的RGC死亡,从而为未来的治疗研究铺平了道路。