The Aging Eyes Study: mitochondrial dysfunction as a driver of age-related vision loss

Abstract
The aging of the eyes is a phenomenon that many of us take as a given as we age, vision loss
and the subsequent impacts on daily life - less physical activity, higher risk of depression,
higher risk of falls, more rapid cognitive function decline - considered immutable
consequences of the aging process. Age-related vision loss results from myriad pathways but
systemic inflammation and oxidative stress may be a common underlying factor. Not
everyone will develop eye disease, though most experience vision changes with age. The vital
question is: are there ways to distinguish between individuals along the continuum from
normal age-related changes to faster deterioration of vision function to overt pathology?
Having an indicator of underlying pathological processes that contribute to faster aging of the
eyes would have a large impact on screening and vision care as well as identify high risk
groups for clinical trials. Mitochondria, which are central to the production of adenosine
triphosphate (ATP), to the regulation of bioenergetic processes, and to various signaling
pathways, are susceptible to oxidative stress, resulting in loss of efficiency in oxidative
phosphorylation. Mitochondrial damage is a major contributor to age-related diseases
through cell apoptosis, dysregulated energy production, and inflammation. Mitochondrial
function is increasingly thought to be an important indicator of systemic aging, and
mitochondrial diseases frequently involve a range of ophthalmic manifestations. We
hypothesize that mitochondrial function and genetics may provide a marker of the biological
aging of the eyes as well as provide information on susceptibility to pathologic damage
leading to disease. Through this project, we will identify the role of mitochondrial function
and genetics in the etiology of aging-related eye diseases. We will build a platform and foster
existing collaboration to further investigate the role of mitochondrial function in age-related
eye diseases. Lastly, this project will generate knowledge for the development of both
mitochondrial function-based clinical indicators of age-related vision loss and provide an
evidentiary base for potential interventions on modifiable aspects of mitochondrial function
that could slow the aging of the eyes to improve vision health.

Grant Number: 1R21EY036435-01
NIH Institute/Center: NIH
Principal Investigator: ALISON ABRAHAM