Abstract
Purpose :
The goal of this study is to determine the effect of apolipoprotein A-I binding protein (AIBP) on visual function in a mouse model of oxidative stress and investigate AIBP-mediated mitochondrial protection in Müller glia against oxidative stress.
Methods :
10 month-old C57BL/6J and AIBP knock out mice were treated with the repeated doses of paraquat (PQ) by intraperitoneal injections, thrice a week (Day 1, 3, 5). On Day 8, Spatial visual function was assessed on a virtual optomotor system, and mitochondrial biogenesis, dynamics and oxidative phosphorylation (OXPHOS) were measured by western blot analysis. rMC1, an immortalized Müller glia cell line, was cultured in Dulbecco’s MEM with 5% FBS. The cells were pretreated for 2 h with recombinant AIBP protein (rAIBP; 0.2 mg/ml), followed by stimulation PQ (500 mM) for 6 or 24 h.
Results :
We found that PQ-induced oxidative stress significantly decreased AIBP expression and the relevant protein expression for mitochondrial biogenesis (PGC-1a and TFAM), dynamics (DRP1 and OPA1), and OXPHOS complex in the retina of 10-month-old C57BL/6J mice. Compared to PQ-treated wild-type (C57BL/6J) mice, AIBP deficiency exacerbated the reduced expression levels of proteins for mitochondria biogenesis, dynamics, and OXPHOS. In addition, AIBP deficiency highly activated GSK-3b, which regulates mitochondrial fission by regulating the dephosphorylation of DRP1 at serine 637. Using Seahorse analysis, we found that AIBP deficiency significantly reduced mitochondria respiratory function and ATP production in oxidative stress-induced rMC1 cells. In addition, oxidative stress induced NLRP3 inflammasome activation. However, treatment of rAIBP significantly prevented mitochondrial dysfunction and mitochondria-dependent inflammasome activation in rMC-1 cells against oxidative stress.
Conclusions :
These results demonstrate that AIBP deficiency exacerbates mitochondrial dysfunction in oxidative stress-induced retina and that administration of AIBP is protective in Müller glia cells against oxidative stress and neuroinflammation. Thus, AIBP could be a therapeutic target for treating glaucoma
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.