The long-term goal of the proposed research is to reveal functions and mechanisms of neuron-glia interaction in visual systems. As previous studies on vision have mostly been focused on the visual transduction cascades and the neuronal circuits, our knowledge about the role of glial cells in visual signaling is still very limited. Intriguingly, glial cells express receptors for neurotransmitters of visual interneurons in both mammalian and fly eyes. It is unknown whether glial cells directly communicate with those neurons for regulation of visual signaling. In our preliminary studies on Drosophila vision, we found that the visual epithelial glia may concentrate a glutamate-gated chloride channel GluCl in 'gnarl', a special glial membrane structure that typically interposes between a glutamatergic interneuron amacrine cell and its postsynaptic partner T1 cell. When the glutamate release from amacrine cell was blocked, the speed of photoreceptor repolarization at the end of light response reduced significantly. Importantly, this visual defect was phenocopied by knocking down the GluCl expression specifically in the epithelial glia, and was also observed in an ADAM protein mutant of impaired gnarl structure. Based on these observations, we propose the existence of a photoreceptor-amacrine cell-epithelial glia-photoreceptor feedback loop, which functions to reinforce the speed of photoreceptor repolarization and is thus important for the temporal resolution of vision. Using a combination of molecular and cell biological, genetic, histological, and electrophysiological approaches, we propose to further investigate this novel function of visual epithelial glia. Specifically, we will 1. Test the hypothesis that laminar epithelial glia receive neuronal input through the glutamate-gated chloride channel GluCl; 2. Test the hypothesis that an ADAM protein MMD is required to localize GluCl in the gnarl structure for the neuron-glia signaling; 3. Identify the mechanism of epithelial glia-mediated photoreceptor regulation. These studies are not only important to visual biology, but will also contribute to our understanding of glial function in general.

Public Health Relevance

Visual glia cells are essential for retinal neuron development and protection, and are implicated in a variety of retinopathies. In this proposal we plan to use the Drosophila eye as a genetic model to study how visual glia interact directly with neurons and how they reciprocally regulate the activity of each other. Findings from this study may provide valuable clues to therapeutic designs directed to prevent degeneration of retinal neurons.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021796-03
Application #
8626400
Study Section
Cellular and Molecular Biology of Glia Study Section (CMBG)
Program Officer
Neuhold, Lisa
Project Start
2012-04-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
3
Fiscal Year
2014
Total Cost
$403,025
Indirect Cost
$158,025
Name
University of Massachusetts Medical School Worcester
Department
Biology
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655
Luan, Zhuo; Reddig, Keith; Li, Hong-Sheng (2014) Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration. Exp Neurol 261:791-801
Chaturvedi, Ratna; Reddig, Keith; Li, Hong-Sheng (2014) Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila. Proc Natl Acad Sci U S A 111:2812-7