Myopia (short-sightedness) results from a failure of emmetropization in which eyes grow too long for their optical power. Myopia's association with sight-threatening complications and near-epidemic prevalence in several populations make it critical that effective treatments for slowing myopia progression be developed. The chick eye has provided a very fruitful model, yielding evidence for local retinal control of eye growth, identifying multifocal (MF) optical manipulations that inhibit ocular elongation as potential myopia treatments, and providing initial insights into the mechanism underlying atropine's anti-myopia action. The guinea pig, a mammalian model with a fibrous sclera more like human sclera, has yielded valuable translational data. Our proposal relied on recent findings from many labs, including our own, to develop a multi-pronged approach to myopia control. It exploits novel tools and advanced technologies to pursue 4 aims: (1) We will use our novel optical imaging (cone) devices and MF spectacle lenses combined with neurotoxins to further investigate the mechanisms underlying MF lens effects on eye growth, and the variables influencing treatment efficacy. (2) We will investigate the anti-myopia actions of atropine, to better understand the roles of retinal and nonretinal mechanisms and to determine effective dosing regimens. (3) We will investigate whether treatment efficacy can be improved by combining MF lenses designed to slow myopic growth with either or both atropine and very bright light, which is also known to slow myopia progression. Experiments under Aim 3 will make use of results from earlier experiments (Aims 1 &2). We will apply molecular biology tools to study retinal/retinal pigment epithelium (RPE) signal pathways. RPE gene expression signatures of myopic and hyperopic growth developed in the last grant period will be exploited to obtain insights into nature of treatment mechanisms and interactions. (4) We will test MF contact lenses in guinea pig to translate our recent related MF spectacle lens studies and look for parallels with chick retinal and RPE molecular signatures that may be applied to understand ocular growth signals.

Public Health Relevance

While promising clinical results with optical and drug treatments have been reported, the best results only slow myopia progression rather than prevent it. This study aims to improve treatment efficacy, with possible outcomes including novel combination treatments involving optical, drug and lighting manipulations. PUBLIC HEALTH RELEVANCE: Most myopia (short-sightedness) represents a failure of emmetropization in which the eye continues to grow after a match between its length and optical power is reached. Myopia's association with sight-threatening complications and near-epidemic prevalence in several populations makes it critical to develop effective treatments for slowing myopia progression. This project will apply modern molecular biology and optical imaging techniques, and functional testing to investigate current and emerging optical, pharmacological and lighting treatment options.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY012392-13A1
Application #
8631608
Study Section
(BNVT)
Program Officer
Wiggs, Cheri
Project Start
1999-01-01
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
13
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Optometry/Opht Tech
DUNS #
City
Berkeley
State
CA
Country
United States
Zip Code
94704
McFadden, Sally A (2016) Understanding and Treating Myopia: What More We Need to Know and Future Research Priorities. Optom Vis Sci 93:1061-3
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
Ostrin, Lisa A; Choh, Vivian; Wildsoet, Christine F (2016) The pattern ERG in chicks - Stimulus dependence and optic nerve section. Vision Res 128:45-52
Zhang, Yan; Raychaudhuri, Suravi; Wildsoet, Christine F (2016) Imposed Optical Defocus Induces Isoform-Specific Up-Regulation of TGFβ Gene Expression in Chick Retinal Pigment Epithelium and Choroid but Not Neural Retina. PLoS One 11:e0155356
Ostrin, Lisa A; Wildsoet, Christine F (2016) Optic nerve head and intraocular pressure in the guinea pig eye. Exp Eye Res 146:7-16
Metlapally, Ravi; Wildsoet, Christine F (2015) Scleral Mechanisms Underlying Ocular Growth and Myopia. Prog Mol Biol Transl Sci 134:241-8
Zhang, Yan; Wildsoet, Christine F (2015) RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia. Prog Mol Biol Transl Sci 134:221-40
McFadden, Sally A; Tse, Dennis Y; Bowrey, Hannah E et al. (2014) Integration of defocus by dual power Fresnel lenses inhibits myopia in the mammalian eye. Invest Ophthalmol Vis Sci 55:908-17
Ostrin, Lisa A; Garcia, Mariana B; Choh, Vivian et al. (2014) Pharmacologically stimulated pupil and accommodative changes in Guinea pigs. Invest Ophthalmol Vis Sci 55:5456-65
Lewis, Jacob A; Garcia, Mariana B; Rani, Lakshmisahithi et al. (2014) Intact globe inflation testing of changes in scleral mechanics in myopia and recovery. Exp Eye Res 127:42-8

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