Abstract
Purpose :
Macular telangiectasia type II (MacTel) is a macular degenerative disease that causes progressive vision loss. While MacTel is predominantly characterized by macular defects, post-mortem eye studies in MacTel patients reveal pan-retinal changes in the retinal pigmented epithelium (RPE), including reduced phagosomes compared to age-matched controls. We have reported that MacTel patients exhibit low circulating levels of serine and glycine. The impact of these non-essential amino acids on RPE function is unknown. The purpose of this study was to assess the impact of reduced serine and glycine on RPE phagocytic function.
Methods :
To assess RPE phagocytic function, we cultured human fetal RPE cells in serine- and glycine-free media, measured expression of endosomal markers, and quantified phagocytic capacity via flow cytometry and imaging. To assess the impact of reduced circulating serine and glycine levels on RPE in vivo we aged mice on a serine- and glycine-free diet and quantified RPE phagosomes using electron microscopy.
Results :
We found decreased phagocytic function in human fetal RPE cells after culture in serine- and glycine-free media. Interestingly, these cells also had elevated expression of endosomal markers. Mice aged on a serine and glycine-free diet had fewer phagosomes in their RPE, recapitulating what was observed in MacTel patients.
Conclusions :
RPE phagocytic capacity is disrupted when serine and glycine availability is reduced, both in vitro and in vivo. This suggests that the reduced levels of circulating serine and glycine observed in MacTel patients may be a contributing factor to RPE dysfunction and macular disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.