Abstract
Purpose :
Retinal neovascularization (RNV) related disease is the leading cause of irreversible blindness in the world. As an anti-inflammatory and anti-cancer agent, the effects of Madecassic acid (MA) against RNV remain unclear. In this study, we investigated whether MA could attenuate RNV in OIR mice model by inhibiting ATF4-CHOP pathways.
Methods :
OIR mice were intraperitoneal injected with MA (50mg/kg) from postnatal (P) 12 to P17. RNV area was detected by retinal flat-mount and immunofluorescence staining. Retinal ganglia cell apoptosis was evaluated with TUNEL staining, and the expression of apoptosis- and endoplasmic reticulum (ER) stress-related molecules were detected by western blotting and RT-PCR. The activation of ATF4-CHOP pathway was evaluated with western blotting and immunofluorescence staining.
Results :
After treated with MA, the areas of RNV were markedly decreased and TUNEL-positive cell ratio was significantly reduced in OIR mice. And MA also attenuated hypoxia-induced ER stress as shown by a reduced expression of apoptosis- and endoplasmic reticulum stress-related molecules, such as IRE1a, p-PERK, p-eIF2a and cleaved-caspase-12. Moreover, the elevated expressions of CHOP, ATF4 in retinas of OIR mice were all reduced after MA treatment.
Conclusions :
The current study indicated that the regulation of apoptosis and ER stress by MA would be a promising therapy to reverse the process and development of RNV.
This is a 2020 ARVO Annual Meeting abstract.