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.
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.
|El-Nimri, Nevin W; Wildsoet, Christine F (2018) Effects of Topical Latanoprost on Intraocular Pressure and Myopia Progression in Young Guinea Pigs. Invest Ophthalmol Vis Sci 59:2644-2651|
|Garcia, Mariana B; Jha, Amit K; Healy, Kevin E et al. (2017) A Bioengineering Approach to Myopia Control Tested in a Guinea Pig Model. Invest Ophthalmol Vis Sci 58:1875-1886|
|Wang, Kevin K; Metlapally, Ravikanth; Wildsoet, Christine F (2017) Expression Profile of the Integrin Receptor Subunits in the Guinea Pig Sclera. Curr Eye Res 42:857-863|
|E Bowrey, Hannah; Zeng, Guang; Y Tse, Dennis et al. (2017) The Effect of Spectacle Lenses Containing Peripheral Defocus on Refractive Error and Horizontal Eye Shape in the Guinea Pig. Invest Ophthalmol Vis Sci 58:2705-2714|
|Zhang, Yan; Liu, Yue; Hang, Abraham et al. (2016) Differential gene expression of BMP2 and BMP receptors in chick retina & choroid induced by imposed optical defocus. Vis Neurosci 33:E015|
|Ostrin, Lisa A; Wildsoet, Christine F (2016) Optic nerve head and intraocular pressure in the guinea pig eye. Exp Eye Res 146:7-16|
|Zhang, Yan; Raychaudhuri, Suravi; Wildsoet, Christine F (2016) Imposed Optical Defocus Induces Isoform-Specific Up-Regulation of TGF? Gene Expression in Chick Retinal Pigment Epithelium and Choroid but Not Neural Retina. PLoS One 11:e0155356|
|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|
|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|
|McFadden, Sally A (2016) Understanding and Treating Myopia: What More We Need to Know and Future Research Priorities. Optom Vis Sci 93:1061-3|
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