Bushen-Huoxue-Mingmu-Formula attenuates pressurization-induced retinal ganglion cell damage by reducing mitochondrial autophagy through the inhibition of the Pink1/Parkin pathway.

Background: Bushen-Huoxue-Mingmu-Formula (MMF) has achieved definite clinical efficacy. However, its mechanism is still unclear.

Objective: Investigating the molecular mechanism of MMF to protect retinal ganglion cells (RGCs).

Methods: This study developed a pressurization-induced model of damaged RGCs, which were then treated with a serum supplemented with MMF. The effects of MMF on proliferation, apoptosis, adenosine 5'-triphosphate content, and mitochondrial structure of RGCs were investigated, and the underlying molecular mechanism was explored by RNA interference experiment.

Results: In the pressurization-induced RGC injury model, apoptosis rate increased, cell proliferation decreased, adenosine 5'-triphosphate content reduced, mitochondrial structure was disrupted, BCL2-associated X, cleaved caspase-3, and microtubule-associated proteins light chain 3 II/I protein expression enhanced, B cell lymphoma-2 and p62 protein expression decreased, and the Pink1/Parkin pathway was activated. The stress-induced damage to RGCs was, however, reversible following MMF-mediated inhibition of the Pink1/Parkin pathway. Pink1 short-hairpin RNA downregulated Pink1 expression in RGCs, which led to outcomes that aligned with those observed with MMF intervention.

Conclusions: MMF altered the expression of apoptosis- and autophagy-related proteins and possibly inhibited the Pink1/Parkin signaling pathway, which led to reduced pressurization-induced mitochondrial autophagy in RGCs. This preventive effect of MMF on RGCs can be potentially useful to preserve the viability of RGCs.