Emmetropization is the regulatory process that normally matches the optical power of the eye to its length, so that objects can be focused on the retina. Abnormalities can cause myopia (shortsightedness), in which the eye grows too long for its optical power, leading to sight-threatening complications. Refractive surgery that overcorrects myopia may lead to renewed eye growth, as may certain lighting conditions. Near-epidemic prevalence of myopia in several populations makes it critical and timely to understand the determinants of emmetropization, without which effective treatments are unlikely. Studies: The chick eye has proven to be an effective experimental model for emmetropization: many optical, surgical and pharmacological manipulations can be performed, with time and cost effectiveness, and results generalize well to mammals and primates. Our recent studies in the chick used optic nerve section (ONS) to dissociate retina and brain, and suggested that emmetropization is largely controlled locally, by the retina. Emmetropization with ONS is abnormal. We ask whether this is due to cell loss and retinal rewiring, which are side effects of ONS.
Aim 1 (Role of inner retinal cells in emmetropization): We will (a) dissociate retina and brain with a ganglion cell toxin that spares certain fibers destroyed by ONS, (b) use molecular markers to test if ONS causes loss of glucagonergic amacrine cells, and (c) use growth factors to protect ganglion cells in ONS eyes. Visual stimuli are well known to affect posterior segment growth. What determines corneal growth? Aim 2 (Role of the retina in anterior segment growth): We will (a) measure effects of continuous light on corneal flattening, and consequent posterior chamber growth, (b) use radial keratotomy to control for effects of non-visually induced corneal flattening, and (c) measure intersegmental fluid exchange as a potential conduit for retinal factors that control corneal growth. It is still not known how the retina distinguishes the sign of a defocused image.
Aim 3 (Decoding defocus in emmetropization): We will manipulate defocus cues with (a) reverse chromatic aberration lenses, (b) blue and red monochromatic rearing, and (c) optical control of object distance, spatial frequency, contrast, and monochromatic aberrations. Reduced retinal acuity may explain the high refractive errors in congenital outer retinal pathologies.
Aim 4 (Retinal acuity & emmetropization): We will study in 3 low-acuity preparations: (a) albino chicks, (b) normal chicks reared in UV light, and (c) normal chicks reared in dim light.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012392-07
Application #
6927828
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Oberdorfer, Michael
Project Start
1999-01-01
Project End
2007-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
7
Fiscal Year
2005
Total Cost
$255,252
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Optometry/Ophthalmol
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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
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
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
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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