Age-related macular degeneration, glaucoma and cataract are major causes of vision loss and all three diseases are age-related. Each is associated with the accumulation of senescent cells in, respectively, the retinal pigmented epithelium, the retinal ganglion cells, and the lens epithelium, and mouse model studies indicate that senescent cells contribute to the occurrence and progression of these eye diseases. Senescent cells are abnormal cells that accumulate during aging, fail to divide and instead have disruptive effects on tissue function. Recent research indicates that senescent cells are aneuploid ie have chromosomal abnormalities. Aneuploid cells can be removed from developing tissues and preliminary data indicates that other cells recognize them based on imbalanced ribosomal protein gene dose. Genetic screens will be performed in fruitfly eyes to isolate gene mutations that act in normal cells to prevent their recognizing and eliminating aneuploid cells. Whole genome sequencing and mapping methods will be used to identify the genes affected by these mutations, which will provide insight into the molecular mechanisms of aneuploid cell recognition and removal. It is anticipated that these studies can help understand how senescent cells accumulate to cause age-related macular degeneration, glaucoma and cataract, and suggest approaches to reduce the incidence and progression of these eye disases.

Public Health Relevance

Age-related macular degeneration, glaucoma and cataract are major causes of vision loss in older people. This project will use novel genetic screens to help understand how abnormal cells can be removed and why they accumulate in aging eye tissues to cause these diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY032256-01
Application #
10110705
Study Section
Development - 1 Study Section (DEV1)
Program Officer
Araj, Houmam H
Project Start
2021-01-01
Project End
2022-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
University-Wide
DUNS #
081266487
City
Bronx
State
NY
Country
United States
Zip Code
10461