NIH researchers 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, details how alterations in a factor called AKT2 affects the function of lysosomes and results in the production of drusen deposits in the retina, a hallmark sign of dry age-related macular degeneration (AMD). 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.
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, which act as the cells’ garbage disposals. 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.
The researchers manipulated AKT2 expression levels in the RPEs of mice. When they overexpressed AKT2, lysosomes lost normal function and the mice developed dry AMD symptoms such as RPE degeneration. The researchers observed similar features in RPE cells from human donors with AMD and 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.
This study’s findings form the basis for a possible future treatment for dry AMD, for which no therapy currently exists. AMD is one of the most common causes of vision loss in the U.S. People with dry AMD develop drusen in an area of the light-sensing retina called the macula that people use for sharp, central vision.
The study builds upon previous work published NEI’s Section on Ocular Stem Cell and Translational Research Section.
The NIH Record, founded in 1949, is the biweekly newsletter for employees of the National Institutes of Health.
Published 25 times each year, it comes out on payday Fridays.
Editor: Dana Talesnik
Dana.Talesnik@nih.gov (link sends e-mail)
Assistant Editor: Eric Bock
Eric.Bock@nih.gov (link sends e-mail)
Staff Writer: Amber Snyder
Amber.Snyder@nih.gov (link sends e-mail)
NIH…Turning Discovery Into Health®
National Institutes of Health
9000 Rockville Pike
U.S. Department of Health and Human Services (link is external)