Targeting Eye Immune Cells to Prevent Glaucoma-Induced Nerve Damage

The aim of this project is to learn how immune cells in the eye contribute to nerve damage in glaucoma and test molecules that might prevent it.

The high fluid pressures in the eye with glaucoma can damage the optic nerve, which transmits signals from the retina to the brain. Microglia are immune cells in the retina that contribute to this injury quite early on through their responses to inflammation. Shubham Maurya, PhD, and his colleagues are working with naturally occurring small molecules that may dampen this reaction from the microglia.

For this work, they plan to use lab models to test how these small molecules put the brakes on microglia. With cutting-edge molecular tools, the researchers will pinpoint exactly when microglia start showing this damaging reaction and how the transition to damage mode takes place. Part of this work will involve sorting out how other support cells in the retina called astrocytes produce these small molecules and usually keep microglia in check.

The results are predicted to offer insights into the early events that lead to damage by microglia and the role of astrocytes in limiting this response. Dr. Maurya and his coworkers expect the findings to highlight new candidate treatment approaches for glaucoma.

This project will use cutting-edge techniques such as scRNAseq, LC/MS/MS-lipidomics, and automated morphometric analysis of microglia to comprehensively characterize microglial activation and regulation in glaucoma. Additionally, the project will utilize a novel mouse line to selectively delete lipoxin formation in astrocytes and investigate the role of the endogenous astrocyte lipoxin pathway in maintaining microglia homeostatic function in OHT. Finally, it will provide valuable insights into the early events leading to microglial activation and the potential therapeutic targets for glaucoma.

The completion of this study will provide a better understanding of the mechanisms underlying microglial activation in glaucoma and the role of the endogenous astrocyte lipoxin pathway in maintaining microglia homeostasis. This knowledge can potentially lead to the development of new therapeutic targets for treating glaucoma, a leading cause of irreversible blindness worldwide. Additionally, this study can pave the way for developing novel treatment strategies for other neurodegenerative diseases involving microglial activation.