The rapid increase in myopia prevalence over the last 30 years suggests a role for the environment in controlling refractive development. Accumulating evidence suggests that ambient light (e.g. sunlight) affects eye growth during childhood by dopamine signaling. However, the characteristics of visual stimuli and underlying retinal signals that regulate refractive development remain elusive. In this proposal, the knowledge gap concerning whether retinal ?gain adjustment? pathways for ambient irradiance may alter myopia susceptibility will be addressed. Preliminary data shows that both dim and bright light are protective for lens- induced myopia in mice and that myopic children spend less time in both dim and bright light. Furthermore, dopamine activity is differentially modulated by an interaction effect of exposure to variable ambient lighting and lens defocus. Thus, the hypothesize that retinal ?gain adjustment? to ambient light determines an organism?s susceptibility to myopia through dopamine signaling will be tested. It is proposed that retinal detection of irradiance occurs through non-classical retinal pathways that have been reported to detect light across a broad range of ambient conditions from starlight to sunlight. This proposal will determine which photoreceptor pathways modulate the protective effects of scotopic and photopic light on lens induced myopia and the role of dopamine signaling by pursuing three specific aims using mouse models.
Aim 1 will evaluate if rod pathway stimulation drives dopamine release and decreases myopic refractions under dim and bright ambient conditions.
Aim 2 will investigate if retinal transmission through Cx36 gap junctions provides protective effects for LIM in dim and bright light via increased dopamine release.
Aim 3 will determine whether ipRGCs modulate refractive development by detecting visual stimuli under a full range of ambient conditions. The expected outcomes will increase our knowledge of basic retinal dopamine signaling and further elucidate the mechanisms underlying myopic eye growth. These results are expected to foster the development of new therapeutic interventions for the growing number of myopic children.

Public Health Relevance

The prevalence of myopia or near-sightedness is increasing at alarming rates and us predicted to reach 50% worldwide by 2050. We urgently need to understand the mechanisms driving this increased eye growth in order to develop effect interventions that prevent or ameliorate myopia. The proposed research will elucidate the retinal pathways that modulate refractive eye growth under ambient lighting conditions, like bright, outdoor light, in order to develop new therapeutic strategies for myopia.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY016435-11
Application #
9765501
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Wiggs, Cheri
Project Start
2009-01-01
Project End
2023-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
11
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Georgia Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30318
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Metlapally, Ravikanth; Park, Han Na; Chakraborty, Ranjay et al. (2016) Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse. Invest Ophthalmol Vis Sci 57:6089-6097
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Prunty, Megan C; Aung, Moe H; Hanif, Adam M et al. (2015) In Vivo Imaging of Retinal Oxidative Stress Using a Reactive Oxygen Species-Activated Fluorescent Probe. Invest Ophthalmol Vis Sci 56:5862-70

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