University of Nebraska researchers show role of cytokines in retinal cells

September 6, 2024

GlaucomaRetina

Basic Research

Grantee

New research from a University of Nebraska Medical Center (UNMC) ophthalmology team demonstrates for the first time that cytokines - the cell-signaling proteins known to regulate inflammation in response to disease or injury - play an important role in the development and regeneration of the retinal cells that degenerate in glaucoma.

The findings, published recently in the journal Stem Cell Reports, suggest microglia, the resident immune cells in the retina that secrete cytokines, as a potential cellular target for glaucoma therapeutics, said Iqbal Ahmad, Ph.D., professor in the UNMC Department of Ophthalmology and Visual Science.

Ahmad led the study team with the lead author Murali Subramani, Ph.D., a postdoctoral research associate, and Brandon Lambrecht. Their article, "Human Microglia-derived Proinflammatory Cytokines Facilitates Human Retinal Ganglion Cells Development and Regeneration," was published Aug. 13.

Glaucoma is the second largest cause of blindness, affecting 3 million people in the U.S. and 80 million people worldwide, Ahmad said. And there is no cure for degeneration of retinal ganglion cells (RGCs), he said.

The research team is studying why and how RGCs degenerate in hopes of developing early diagnostics and therapeutics, Ahmad said.

Using the stem cell model of retinal development, Subramani and Lambrecht demonstrated that cytokines secreted by microglia promoted the growth of RGC axons, which connect the retina with the higher centers in the brain for the perception of vision.

When these axons were experimentally damaged to simulate RGC degeneration in glaucoma, the microglia-derived cytokines facilitated their regeneration.

"Our observations offer a new way to look at cytokines secreted by microglia," Ahmad said. "We found that these chemicals are not always proinflammatory but have developmental function where they ensure the functional maturity of RGCs and the proper growth of their axons, both necessary for visual perception."

Future therapeutics, Ahmad said, could include recapitulating the developmental function of microglia to counteract the RGC degeneration in glaucoma.

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