Vitamin A is critical for human health and vision. Insufficient uptake of vitamin A severely damages photoreceptors, causes a loss of visual pigments, and is the leading cause of preventable childhood blindness according to the WHO. However, little is known about how vitamin A deprivation affects photoreceptors on the molecular level and how vitamin A replacement therapy mediates structural and functional photoreceptor recovery. Our long-term goal is to use the Drosophila melanogaster retina as a model to fill this gap in our knowledge and to analyze the underlying mechanisms. This proposal synergistically combines Drosophila genetics, immunohistochemistry, behavioral analysis, and quantitative proteomics. This multidisciplinary approach will allow us to evaluate the central hypotheses that different photoreceptor types ? functionally equivalent to human rods and cones - respond differently to vitamin A deprivation and that vitamin A deficiency triggers protective mechanisms that stabilize damaged photoreceptors. We will pursue three major specific aims. First, we will analyze how different photoreceptor types respond to vitamin A deprivation. Second, we seek to identify the proteins and cellular pathways that are affected by vitamin A deprivation and vitamin A replacement therapy. Third, we will determine the function of a novel transmembrane protein that we found to be highly upregulated in vitamin A-deprived retinas to stabilize the damaged photoreceptors. The proposed research is significant, as it will provide fundamental insights into the molecular response of different photoreceptor types to vitamin A deprivation. It will also unravel how vitamin A replacement therapy leads to improvement of photoreceptor structure and function. Collectively, this proposal has the potential to identify mechanisms that stabilize damaged photoreceptors and to open new avenues for treating human eye diseases.

Public Health Relevance

Vitamin A is critical for human vision and according to the World Health Organization, vitamin A deficiency is the leading cause for preventable childhood blindness. The proposed research uses Drosophila melanogaster as a model to analyze how different photoreceptor types are affected by vitamin A deprivation and how they recover upon vitamin A replacement therapy. This proposal has the potential to discover novel molecular mechanisms that promote photoreceptor survival and thus could serve to treat human eye diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY029659-03
Application #
10067548
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Neuhold, Lisa
Project Start
2019-01-01
Project End
2023-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Massachusetts Boston
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
808008122
City
Boston
State
MA
Country
United States
Zip Code