New Target Identified for Dry AMD Treatment

NIH Researchers Uncover Key to Dry AMD

Researchers from the National Institutes of Health (NIH) and Johns Hopkins University have identified a crucial factor in the development of dry age-related macular degeneration (AMD), a leading cause of vision loss. Their study, published in Nature Communications, reveals that dysfunction in the lysosomal degradation process of retinal cells is driven by alterations in the protein AKT2.

Cellular Pathology of Dry AMD

The research highlights how changes in AKT2 affect lysosome function within the retinal pigment epithelium (RPE) cells. Lysosomes, often described as the cell's garbage disposals, are essential for maintaining the health of the retina. In the case of dry AMD, these organelles fail to properly process waste, leading to the accumulation of drusen—a characteristic sign of the disease. The team found that manipulating AKT2 expression in mice led to lysosomal dysfunction and dry AMD symptoms, such as RPE degeneration. Similar dysfunction was observed in human RPE cells from AMD patients and those with a gene variant known as CFH Y402H, which increases AMD risk.

Potential for New Therapeutics

This discovery suggests that targeting AKT2 and its pathway could open new avenues for treating dry AMD, for which there are currently no effective therapies. The study builds on earlier work by Dr. Ruchi Sharma, who developed an AMD patient stem cell-derived RPE model that further supports these findings.

Highlights

• NIH and Johns Hopkins researchers identified AKT2 as a key factor in dry AMD.
• AKT2-related dysfunction in lysosomes leads to drusen formation.
• Research in mice and human cells shows potential for targeting AKT2 in future treatments.
• Dry AMD, characterized by drusen in the macula, currently lacks effective therapies.
• The study builds on previous AMD research by Dr. Ruchi Sharma.

Reference

Ghosh S, Sharma R, et al. "The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in non-neovascular AMD." Nat Commun. 2024 Jul 21;15(1):6150. doi: 10.1038/s41467-024-50500-z.

Sharma R, et al. "Epithelial phenotype restoring drugs suppress macular degeneration phenotypes in an iPSC model." Nat Commun. 2021 Dec 15;12(1):7293. doi: 10.1038/s41467-021-27488-x.

Dara source：https://www.nih.gov/news-events/news-releases/nih-researchers-discover-potential-therapeutic-target-degenerative-eye-disease