Silencing miR-126-5p protects trabecular meshwork cells against chronic oxidative injury by upregulating HSPB8 to activate PI3K/AKT pathway.

Chronic oxidative stress (COS) is related to the pathophysiology of the trabecular meshwork (TM) in glaucoma. MicroRNAs (miRNAs) have a key role in the oxidative stress-mediated glaucoma. This work investigated the function of miR-126-5p in human trabecular meshwork cells (TMCs) under chronic oxidative stress (COS). The miR-126-5p inhibitor was transfected into TMCs to assess the function of miR-126-5p. The targets of miR-126-5p were predicted by bioinformatic analysis. A luciferase assay was applied to test the relationship between miR-126-5p and its target. Cell proliferation was assessed using MTT. Flow cytometry and TUNEL were used for the assessment of apoptosis. We found that the miR-126-5p level was elevated in TMCs exposed to COS. MiR-126-5p inhibitor markedly promoted TMC proliferation and inhibited the increases in apoptosis and extracellular matrix (ECM) proteins induced by COS. Heat shock protein B8 (HSPB8) was identified to be targeted by miR-126-5p. MiR-126-5p inhibitor restored the expression level of HSPB8 in TMCs under COS. Additionally, miR-126-5p depletion activated PI3K/AKT signaling in TMCs by upregulating HSPB8. HSPB8 downregulation or LY294002 treatment prevented the effects mediated by miR-126-5p inhibition on apoptosis and ECM in COS-treated TMCs. Overall, silencing miR-126-5p protects TMCs against COS-induced injury by upregulating HSPB8 to activate PI3K/AKT signaling.