Emmetropization is the regulatory process that matches the eye's length to its optical power, bringing distant objects to focus on the retina with accommodation relaxed. Myopia, or shortsightedness, is the failure of emmetropization in which the eye grows too long for its optical power. Myopia's association with sight-threatening complications, and near-epidemic prevalence in several populations, make it critical to understand the determinants of emmetropization, without which effective treatments are unlikely to be developed. The chick eye has provided a very fruitful model of emmetropization, clarifying the optical conditions that lead to myopia, providing evidence for local retinal control of eye growth, and identifying optical manipulations that inhibit eye elongation, which are therefore potential myopia treatments.
Aims and Studies: (1) We will study local molecular signaling across the retinal pigment epithelium (RPE), which separates the image-processing retina from the choroid and eye shape-determining sclera, using molecular techniques to delineate patterns of gene expression in eyes undergoing experimentally altered growth through exposure to myopic and hyperopic defocus, and in cultured RPE treated with presumptive retinal growth modulators. We will then conduct in vivo tests of growth factors identified in gene expression studies. (2) We will use these genetic signatures, in combination with drugs known from previous work to modulate responses to imposed myopia and hyperopia, to study the mechanisms of eye growth induced by simultaneous, competing myopic and hyperopic defocus produced by several types of multifocal and astigmatic lenses. We will evaluate hypotheses regarding retinal processing, optical aberrations, and peripheral retinal growth to explain lens effects. (3) We will develop a guinea pig model to extend our findings on local ocular growth regulation to mammalian eyes, and to compare mammalian and avian responses to simple and competing defocus stimuli.
Emmetropization is the regulatory process that matches the eye's length to its optical power, bringing distant objects to focus on the retina with accommodation relaxed. Myopia, or shortsightedness, represents the failure of emmetropization in which the eye grows too long for its optical power, in near-epidemic prevalence in several populations, with associated sight-threatening complications, making it critical to understand the determinants of emmetropization, without which effective treatments are unlikely to be developed. This project will apply modern molecular biology and optical techniques to investigate the mechanisms underlying emmetropization, with a view to developing novel treatments for myopia.
|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|
|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|
|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|
|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|
|Zhang, Yan; Wildsoet, Christine F (2015) RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia. Prog Mol Biol Transl Sci 134:221-40|
|Metlapally, Ravi; Wildsoet, Christine F (2015) Scleral Mechanisms Underlying Ocular Growth and Myopia. Prog Mol Biol Transl Sci 134:241-8|
|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|
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