Researchers from the National Institutes of Health (NIH) have discovered the source of dysfunction in the process whereby cells in the eye’s retina remove waste.

A report by scientists at NIH and Johns Hopkins University, Baltimore, has detailed how alterations in a factor called AKT2 affects the function of organelles called lysosomes, resulting in the production of drusen, a hallmark sign of dry age-related macular degeneration (AMD).1 According to the researchers, the findings suggest drusen formation is a downstream effect of AKT2-related lysosome dysfunction and points to a new target for therapeutic intervention.

Lysosomes are like cells’ garbage disposals, and they play a crucial role in maintaining the eye’s light-sensing retina. Key cells that make up the retinal pigment epithelium (RPE) provide oxygen and nutrients to the retina’s energetically active neurons. They also collect and process the retina’s waste products through lysosomes. Failure in the cells’ ability to process these waste products leads to the formation of drusen. As AMD progresses, drusen increase in number and volume. But despite intensive research, drusen formation is still largely a mystery.

In mice, the researchers manipulated AKT2 expression levels in RPE. When they overexpressed AKT2, lysosomes lost normal function and the mice developed dry AMD symptoms such as RPE degeneration. The researchers saw similar features in RPE cells from human donors with AMD or in RPE cells generated from patient stem cells. Cells from donors who possessed a gene variant called CFH Y402H, which increases AMD risk, had relatively greater expression of AKT2, showed functionally defective lysosomes, and formed drusen deposits.

The study was led by Dr Kapil Bharti, and Dr Ruchi Sharma, who co-head the Ocular Stem Cell and Translational Research (OSCTR) section within NIH’s National Eye Institute Intramural Research Program. Their findings form the basis for a possible future treatment for dry AMD.

Reference available at mivision.com.au