Permanent visual field loss from glaucoma is a significant cause of blindness worldwide. Many glaucomatous visual field defects begin in the peripheral regions where, without treatment, they gradually enlarge to eventually damage the central high acuity zone that is critically important for normal function. Current medical and surgical treatment can slow the progression of peripheral visual field defects, limiting damage to the central field and preserving functional vision for many glaucoma patients. However, in many glaucoma patients the initial functional defect appears in the central visual field as a paracentra scotoma. Glaucoma patients presenting with early-stage central visual field defects have more difficulty reading, driving and are more likely to become blind from the disease. Importantly, current treatment strategies can not prevent or restore functional vision in patients that develop visual field defects involving the central regions. Recent studies have shown that glaucoma patients with central visual field defects at early stages of the disease have common features defining a glaucoma endophenotype that is likely the result of multiple genetic and/or environmental risk factors. In this proposal we will use a powerful integrated approach to identify genetic risk factors contributing to central vision loss in glaucoma using data from GWAS, whole exome sequencing and pathway analysis. The ultimate goal of this research is to identify genes that predispose to early-stage loss of central vision, making it possible to develop gene-based diagnostic screening tests to identify individuals at risk before irreversible damage has occurred. Additionally, the identification of genes that predispose to central vision loss wil provide insight into the responsible underlying molecular events which could lead to new preventative therapies.

Public Health Relevance

Glaucoma is an intraocular pressure (IOP) related progressive optic neuropathy that ultimately leads to blindness. Permanent visual field loss from glaucoma is a condition of public health significance worldwide, affecting millions of people. Loss of the high acuity central vision is particularly disabling as these individuals have difficulty reading, driving and are more likely to become blind from the disease. The etiology of glaucoma is poorly understood and effective means of primary prevention and curative therapies are not available. The overall goal of our research is to elucidate the molecular pathogenesis of glaucoma making it possible to implement effective screening and prevention strategies and to develop novel therapies. The primary aim of this proposal is to identify genetic variants that significantly contribute to loss of central vision causing early onset of blindness i glaucoma patients.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21EY022766-02
Application #
8622199
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Agarwal, Neeraj
Project Start
2013-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$200,900
Indirect Cost
$78,400
Name
Massachusetts Eye and Ear Infirmary
Department
Type
DUNS #
073825945
City
Boston
State
MA
Country
United States
Zip Code
02114
Loomis, Stephanie J; Kang, Jae H; Weinreb, Robert N et al. (2014) Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 121:508-16
Kang, J H; Loomis, S J; Yaspan, B L et al. (2014) Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond) 28:662-71