Cellular senescence mediates retinal ganglion cell survival regulation post-optic nerve crush injury.

Autor: Yao Y; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Bin X; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Xu Y; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Chen S; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Chen S; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Yuan XL; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Cao Y; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China., Ng TK; Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, China.; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Jazyk: angličtina
Zdroj: Cell proliferation [Cell Prolif] 2024 Dec; Vol. 57 (12), pp. e13719. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1111/cpr.13719
Abstrakt: Traumatic optic neuropathy refers to optic nerve (ON) injury by trauma, including explosion and traffic accident. Retinal ganglion cell (RGC) death is the critical pathological cause of irreversible visual impairment and blindness in ON injury. We previously investigated the patterns of 11 modes of cell death in mouse retina post-ON injury. Here we aimed to identify additional signalling pathways regulating RGC survival in rodents post-ON injury. RNA sequencing analysis identified the upregulation of inflammation and cellular senescence-related genes in retina post-ON injury, which were confirmed by immunoblotting and immunofluorescence analyses. Increased expression of senescence-associated β-galactosidase (SA-βgal) in RGCs and activation of microglia were also found. Transforming growth factor-β receptor type II inhibitor (LY2109761) treatment suppressed p15 Ink4b and p21 Cip1 protein and SA-βgal expression and promoted RGC survival post-ON injury with decreasing the expression of cell death markers in retina. Consistently, senolytics (dasatinib and quercetin) treatments can promote RGC survival and alleviate the reduction of ganglion cell complex thickness and pattern electroretinography activity post-ON injury with reducing SA-βgal, p15 Ink4b , p21 Cip1 , microglial activation and cell death marker expression. In summary, this study revealed the activation of cellular senescence in rodent retina post-ON injury and contribute to RGC survival regulation. Targeting cellular senescence can promote RGC survival after ON injury, suggesting a potential treatment strategy for traumatic optic neuropathy.
(© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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