The incidence of myopia (near-sightedness) has increased in alarming rates over the last 30 years, creating the risk for retinal detachment and costing billions in healthcare dollars for refractive corrections. The rapid increase in myopia suggests that environmental factors may play a key role. We propose that the reason for the accelerating incidence of myopia is the mesopic lifestyle shared by people in modern society. The mechanism driving refractive development has been localized to the retina, but the retinal pathways and biochemical signaling remain unknown. We hypothesize that mesopic illumination levels (indoor lighting) induce myopia by stimulating specific retinal pathways which alter dopamine and melanopsin signaling. This hypothesis is supported by pilot data that shows that scotopic (night sky) and photopic (sunlight) illumination levels reduce lens-induced myopia, while mesopic illumination increases lens-induced myopic shifts. Additionally, a growing number of animal and human studies show protective effects of bright light on myopia development. This hypothesis supports three innovative ideas that will be tested: 1) ambient lighting may establish a tonic, steady state in retinal signaling upon which visual input is processed, such tha scotopic and photoic illumination levels slow myopic eye growth and mesopic illumination promotes myopic eye growth, 2) dopamine signaling underlies these effects such that mesopic illumination produces the lowest level of dopamine bioavailability when combined with disrupted visual input, and 3) melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) may signal eye growth under photopic illumination.
Aim 1 will examine whether different ambient illumination levels alter susceptibility to myopia by measuring refractive error and ocular biometry of mice housed under different lighting conditions with and without lens defocus.
Aim 2 will investigate the role of dopamine modulation under each ambient illumination using genetic and pharmacological approaches to examining dopamine receptors and dopamine metabolism.
Aim 3 will determine whether melanopsin mediates refractive development in each ambient illumination by using melanopsin-deficient mouse models. The results will provide new insights about how rods, cones and ipRGCs regulate visually-driven eye growth through dopamine and melanopsin signaling. These experiments will identify clinically relevant environmental factors that may alter susceptibility to myopia while also providing potential therapeutic drug targets to slow or stop myopia progression.
Uncorrected refractive errors represent the leading cause of blindness in the world and are the focus of the World Health Organization Vision 2020 program. The incidence of myopia continues to increase in the US and other countries, suggesting a potential environmental factor influencing refractive development. The proposed research will test whether the light environment determines susceptibility for myopia and is expected to identify clinically relevant environmental factors and pharmacological targets to prevent myopia progression.
|Chakraborty, Ranjay; Park, Han Na; Tan, Christopher C et al. (2017) Association of Body Length with Ocular Parameters in Mice. Optom Vis Sci 94:387-394|
|Zhou, Xiangtian; Pardue, Machelle T; Iuvone, P Michael et al. (2017) Dopamine signaling and myopia development: What are the key challenges. Prog Retin Eye Res 61:60-71|
|Stone, Richard A; Cohen, Yuval; McGlinn, Alice M et al. (2016) Development of Experimental Myopia in Chicks in a Natural Environment. Invest Ophthalmol Vis Sci 57:4779-89|
|Markand, Shanu; Baskin, Natecia L; Chakraborty, Ranjay et al. (2016) IRBP deficiency permits precocious ocular development and myopia. Mol Vis 22:1291-1308|
|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|
|Bergen, Michael A; Park, Han Na; Chakraborty, Ranjay et al. (2016) Altered Refractive Development in Mice With Reduced Levels of Retinal Dopamine. Invest Ophthalmol Vis Sci 57:4412-4419|
|Chakraborty, Ranjay; Pardue, Machelle T (2015) Molecular and Biochemical Aspects of the Retina on Refraction. Prog Mol Biol Transl Sci 134:249-67|
|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|
|Deming, Janise D; Pak, Joseph S; Brown, Bruce M et al. (2015) Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health. Invest Ophthalmol Vis Sci 56:5407-16|
|Deming, Janise D; Pak, Joseph S; Shin, Jung-A et al. (2015) Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina. Invest Ophthalmol Vis Sci 56:7618-28|
Showing the most recent 10 out of 23 publications