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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012392-12
Application #
8215700
Study Section
Special Emphasis Panel (ZRG1-IFCN-A (04))
Program Officer
Wiggs, Cheri
Project Start
1999-01-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2014-01-31
Support Year
12
Fiscal Year
2012
Total Cost
$347,356
Indirect Cost
$109,756
Name
University of California Berkeley
Department
None
Type
Schools of Optometry/Ophthalmol
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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
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
Aller, Thomas; Wildsoet, Christine (2013) Optical control of myopia has come of age: or has it? Optom Vis Sci 90:e135-7
Zhang, Yan; Liu, Yue; Ho, Carol et al. (2013) Effects of imposed defocus of opposite sign on temporal gene expression patterns of BMP4 and BMP7 in chick RPE. Exp Eye Res 109:98-106
Ostrin, Lisa Anne; Liu, Yue; Choh, Vivian et al. (2011) The role of the iris in chick accommodation. Invest Ophthalmol Vis Sci 52:4710-6
Liu, Yue; Wildsoet, Christine (2011) The effect of two-zone concentric bifocal spectacle lenses on refractive error development and eye growth in young chicks. Invest Ophthalmol Vis Sci 52:1078-86
Tian, Yibin; Tarrant, Janice; Wildsoet, Christine F (2011) Optical and biometric characteristics of anisomyopia in human adults. Ophthalmic Physiol Opt 31:540-9
Ganesan, Prema; Wildsoet, Christine F (2010) Pharmaceutical intervention for myopia control. Expert Rev Ophthalmol 5:759-787
Tarrant, Janice; Roorda, Austin; Wildsoet, Christine F (2010) Determining the accommodative response from wavefront aberrations. J Vis 10:4

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