In a study recently published in Nature Communications, researchers from the National Institutes of Health (NIH) and Johns Hopkins University identified alterations in the enzyme AKT2 as a key driver of lysosome dysfunction in retinal pigment epithelium (RPE) cells, leading to drusen formation, a sign of dry age-related macular degeneration (AMD).

The team, led by Kapil Bharti, PhD, and Ruchi Sharma, PhD, of the NEI’s Ocular Stem Cell and Translational Research Section, found that overexpression of AKT2 in mice resulted in AMD-like symptoms. Similar features were observed in human RPE cells from AMD donors and those generated from patient stem cells. Notably, cells with the Y402H variant of the complement factor H (CFH) gene, which is known to increase AMD risk, showed higher AKT2 expression and impaired lysosome function. This discovery provides new insights into drusen formation mechanisms and suggests a promising avenue for developing treatments for dry AMD.