Microglia, the resident neuroimmune cells of the CNS, play important developmental roles. During embryonic development we showed that retinal microglia target a subset of viable newborn retinal ganglion cells (RGCs) for phagocytic elimination through a process that requires complement signaling. The embryonic retina is a simple system to address how microglia target non-apoptotic cells for phagocytosis, with important implications for the role of microglia in cell loss during injury and disease. To understand the mechanisms of retinal cell elimination, the first aim will address the role of complement expression and stress pathways in RGCs.
The second aim will test specific microglial recognition pathways required for phagocytic retinal cell elimination, including RGCs and astrocytes. This study will shed light on how microglia influence developmental remodeling in the retina, and may ultimately inform our understanding of how microglia participate in retinal disease processes resulting in loss of vision.

Public Health Relevance

Retinal cell number is highly regulated during development, maintained in the healthy retina, but declines in aging and disease leading to loss of vision. Neuron number can be shaped by microglia, which are resident immune cells in the retina and brain. This study will investigate the molecular pathways involved in the elimination of viable retinal ganglion cells during embryonic development, which may yield insight into mechanisms of neuronal loss in retinal injury and disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY031096-01A1
Application #
10073036
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Greenwell, Thomas
Project Start
2020-08-01
Project End
2022-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Utah
Department
Neurosciences
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112