Therapeutic Effect of Aza-PBHA Through Regulated A2E-related Dry Age-Related Macular Degeneration in ARPE-19 Cell and Mice Retina

Abstract

Background: The dry form AMD (dAMD) has been proven that many could observe a high amount of lipofuscin accumulated between the retinal pigment epithelium cells (RPE) and Bruch’s membrane in the retinal layer. Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), the best-characterized lipofuscin fluorophore, has also been reported to lead RPE to autophagy dysfunction. Here, we provided an effective histone deacetylase (HDAC) inhibitor drug, Aza-PBHA (Azp). Due to its potential, we hypothesized that Azp can suppress the blue light-induced accumulation of A2E in dAMD model by regulating the autophagy pathway and accordingly represents the candidate of potential development drug of dAMD.

Purpose: This study aims to evaluate the protective effects of Azp against blue light-induced retinal degeneration and its underlying mechanisms.

Material and Methods: A2E-laden retinal pigment epithelial-19 (ARPE-19) cell damage was used to evaluate the protective effects of Azp on retinal degeneration. MTT assay was used to ensure the impact of Azp in A2E-laden ARPE-19 cells, while the western blot was performed to observe the expressions of autophagy-related marker and investigate the mechanisms of action of Azp. Immunostaining was used to locate the accumulation in the retinal then further evaluate the in vitro and in vivo efficacy.

Results: Azp alleviated the blue light-induced A2E-laden ARPE-19 cell damage, further suppressed the induction of autophagy pathway.

Conclusion: Azp protects against blue light-induced retinal degeneration by modulating A2E-related autophagy pathway.