Normal visual function depends upon the generation of a balanced complement of retinal cell types during development. Although much has been learned about retinal progenitor proliferation and differentiation, little is known about how this s modulated by microglia, which is the resident neuroimmune cell of the central nervous system (CNS). Microglia infiltrates the mouse retina at early stages of eye development and is present by e11.5 coincident with the onset of retinal neurogenesis. However, despite the prevalence of microglia at the earliest stages of neurogenesis and suggestive evidence for a role in cortical neurogenesis, we lack a detailed understanding of whether these cells regulate progenitor cell survival, proliferation or differentiation, particularly in the developing retina. Here we propose o define the pattern of microglia distribution, activation and gene expression changes during retinal development, first by imaging GFP labeled microglia at multiple stages, and then by generating a comprehensive molecular profile of microglia over developmental time. Next we will test whether inhibiting or eliminating microglia alters retinal progenitor proliferation, survval or differentiation. This study will provide a detailed investigation of microglia function during embryonic eye development, and will shed light on the role of neuro-immune interactions on visual system development.

Public Health Relevance

Normal visual function depends upon the generation of a balanced complement of retinal cell types during development, and these processes can be disrupted in pathological situations, such as congenital disorders affecting vision. Microglia are resident immune cells that populate the retina beginning at very early stages of eye development, but their influence on the generation of retinal neurons is poorly understood. This study will investigate microglia function during embryonic eye development, and will shed light on the role of neuro-immune interactions on visual system development.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY025082-02
Application #
8975212
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Greenwell, Thomas
Project Start
2014-12-01
Project End
2016-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
2
Fiscal Year
2016
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
Imai, Hisanori; Misra, Gauri P; Wu, Linfeng et al. (2015) Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats. Invest Ophthalmol Vis Sci 56:7839-46