Down-regulated LAMA4 inhibits oxidative stress-induced apoptosis of retinal ganglion cells through the MAPK signaling pathway in rats with glaucoma

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2019-05, Vol.18 (9), p.932-948
• Main Authors: Wang, Chong, Ren, Ya-Lin, Zhai, Jin, Zhou, Xiao-Yan, Wu, Jing
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - genetics; Cell Survival - genetics; Cells, Cultured; Disease Models, Animal; Down-Regulation - genetics; Glaucoma - metabolism; Hydrogen Peroxide - metabolism; Intraocular Pressure; Laminin - genetics; Laminin - metabolism; Male; Oxidative Stress - genetics; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Research Paper; Retinal Ganglion Cells - metabolism; Signal Transduction - genetics; Transfection
• ISSN: 1538-4101; 1551-4005
• DOI: 10.1080/15384101.2019.1593645

Glaucoma is a neurodegenerative disorder that is generally accepted as the main cause of vision loss. In this study, we tested the hypothesis that laminin α4 (LAMA4) is implicated in glaucoma development by controlling apoptosis of retinal ganglion cells (RGCs) through the mitogen-activated protein kinase (MAPK) signaling pathway. Expression profiles and genes associated with glaucoma were searched to determine the objective gene. Intraocular pressure (IOP) rats model were established and IOP was measured. The mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bcl-2, Bax, Caspase-9, and p53 was determined in concert with the treatment of H O , si-NC, or si-LAMA4 in cultured RGCs. Viability of RGCs, reactive oxygen species (ROS) and cell apoptosis was also measured. LAMA4 was selected as the study object because of its significant difference in two expression profiles. IOP of rats with glaucoma increased significantly after model establishment, and the LAMA4 protein expression in retinal tissue of rats with glaucoma was elevated. Down-regulation of LAMA4 could inhibit the mRNA and protein expression of LAMA4, JNK, p38 MAPK, ERK, Bax, Caspase-9, and p53, as well as restrain the apoptosis and ROS of RGCs, but improve Bcl-2 expression and viability of RGCs. Collectively, the obtained data supported that downregulated LAMA4 might reduce the oxidative stress-induced apoptosis of glaucoma RGCs by inhibiting the activation of the MAPK signaling pathway.