# Aster-B Modulates Oxidative Stress Responses and Carotenoid Distribution in ARPE-19 Cells

## TL;DR

Aster-B helps protect eye cells from stress and controls where carotenoids go, which could impact eye disease.

## Contribution

This study reveals Aster-B's role in lipid transport and stress response in retinal pigment epithelium cells.

## Key findings

- Aster-B improves cell survival under oxidative stress via p53 and TGFβ pathways.
- Carotenoids accumulate in mitochondria in Aster-B-expressing cells.
- Carotenoids' effects on cell survival depend on Aster-B expression and location.

## Abstract

Lipid metabolism and oxidative stress are major contributors to ocular diseases, including drusen formation and photoreceptor damage. Aster-B, encoded by GRAMD1B, mediates the non-vesicular transport of cholesterol and carotenoids and is highly expressed in the human eye, though its specific ocular functions remain unknown. We investigated Aster-B’s role in ARPE-19 cells, a model of the retinal pigment epithelium (RPE), using CRISPR/dCas9 to generate an Aster-B-expressing cell line. Aster-B expression significantly improved cell survival under oxidative stress induced by hydrogen peroxide (H2O2) and was associated with the activation of the p53 and TGFβ signaling pathways, indicating a role in modulating stress responses. To confirm its lipid transport activity, we treated cholesterol-depleted cells with carotenoids and tracked their localization. In Aster-B-expressing cells, carotenoids accumulated in mitochondria, while in control cells, they remained in other cellular compartments. Under oxidative stress, mitochondrial carotenoid levels declined in Aster-B-expressing cells but not in control cells. Interestingly, carotenoids enhanced survival in control cells exposed to H2O2 but had a detrimental effect in Aster-B-expressing cells, suggesting that carotenoid function is context and location dependent. These findings highlight Aster-B’s role in coordinating lipid transport and stress responses in the RPE, with implications for oxidative stress-related eye diseases.