Myeloid cells in retinal and brain degeneration

• Published in: The FEBS journal Vol. 289; no. 8; pp. 2337 - 2361
• Main Authors: Guo, Michelle, Schwartz, Turner D., Dunaief, Joshua L., Cui, Qi N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.04.2022
• Subjects: age‐related macular degeneration; Alzheimer's disease; Animals; brain; Brain - metabolism; Cell death; Central nervous system; Central nervous system diseases; death; Eye diseases; Glaucoma; Glucagon; glucagon-like peptide 1; humans; inflammation; Inflammation - metabolism; Macrophages; Macular degeneration; Microglia; Microglia - metabolism; monocytes; Movement disorders; Myeloid cells; Myeloid Cells - metabolism; Nervous system; Neurodegeneration; Neurodegenerative diseases; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - metabolism; neuroglia; Neurological diseases; Neuroprotection; Neurotoxicity; Optic neuropathy; Parkinson's disease; peripheral nervous system diseases; protective effect; Retina; Retina - metabolism; Retinitis; Retinitis pigmentosa; Retinitis Pigmentosa - metabolism; therapeutics; Uveitis; vision; monocytes; macrophages; Alzheimer’s disease; inflammation; retina; glaucoma; retinitis pigmentosa; age-related macular degeneration; microglia; Parkinson’s disease
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.16177

Retinal inflammation underlies multiple prevalent ocular and neurological diseases. Similar inflammatory processes are observed in glaucomatous optic neuropathy, age‐related macular degeneration, retinitis pigmentosa, posterior uveitis, Alzheimer’s disease, and Parkinson’s disease. In particular, human and animal studies have demonstrated the important role microglia/macrophages play in initiating and maintaining a pro‐inflammatory environment in degenerative processes impacting vision. On the other hand, microglia have also been shown to have a protective role in multiple central nervous system diseases. Identifying the mechanisms underlying cell dysfunction and death is the first step toward developing novel therapeutics for these diseases impacting the central nervous system. In addition to reviewing recent key studies defining important mediators of retinal inflammation, with an emphasis on translational studies that bridge this research from bench to bedside, we also highlight a promising therapeutic class of medications, the glucagon‐like peptide‐1 receptor agonists. Finally, we propose areas where additional research is necessary to identify mechanisms that can be modulated to shift the balance from a neurotoxic to a neuroprotective retinal environment. Myeloid cells can either play a protective role or hasten disease progression in pathogenic processes impacting vision. Mechanistic similarities exist across multiple degenerative diseases including glaucoma, age‐related macular degeneration, retinitis pigmentosa, posterior uveitis, Alzheimer’s disease, and Parkinson’s disease. In addition to reviewing key studies defining important mediators of ocular inflammation, a class of medications with therapeutic promise, the glucagon‐like peptide‐1 receptor agonists, is also highlighted.