It has been found that some animal species become myopic when an eye is exposed to visual deprivation during postnatal development. This environmentally-produced alteration in ocular development can provide information about the mechanisms that normally act to produce emmetropic and ametropic eyes. Studies ar proposed in the present application on a mammalian animal model, thee shrew, to answer several questions: 1) Are there active regulatory mechanism that produce emmetropia? 2) What is the role of accommodation in any regulatory mechanism? 3) Are there local retinal control mechanisms within the eye that do not require a feedback loop through central visual structures? 4) When an eye becomes myopic as a result of environmental manipulations, is the axial elongation due to growth or stretch? Experiment 1 will determine whether rearing with + or - power goggles will result in shorter or longer eyes. In addition, we will explore whether recovery from experimentally-induced myopia can occur after small amounts of myopia have been produced early in the sensitive period. Experiment 2 will determine whether experimentally-induced myopia can develop after removal of accommodation by lesions of either the Edinger-Westphal nucleus or the ciliary ganglion. Experiment 3 will determine whether local retinal control mechanisms exist that can regulate the development of the eye. In these experiments, we will test whether local myopia can result from partial visual field deprivation, whether exposure to strobe-light flashes will prevent lid-suture myopia, and whether lid-suture myopia develops during blockage of afferent visual information with intravitreal tetrodotoxin. Experiment 4 will examine whether the axial elongation in lid-suture myopia occurs through stretch of the sclera as suggested by preliminary data using lathyritic agents to enhance the experimentally-induced myopia. It will also provide a needed dark-rearing control for the lathyritic studies. If the experiments support scleral stretch as a mechanism, in Experiment 5 we will reduce intraocular pressure to determine whether this will decrease the amount of lid-suture myopia. These experiments will significantly advance our understanding of the mechanisms that affect ocular development. If we can learn the mechanisms that produce emmetropia and ametropia in tree shrews, a species closely related to primates, it will then be reasonable to ask whether similar mechanisms control ocular development in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005922-08
Application #
3261628
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-04-01
Project End
1994-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Optometry/Ophthalmol
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
He, Li; Frost, Michael R; Siegwart Jr, John T et al. (2018) Altered gene expression in tree shrew retina and retinal pigment epithelium produced by short periods of minus-lens wear. Exp Eye Res 168:77-88
Gawne, Timothy J; Siegwart Jr, John T; Ward, Alexander H et al. (2017) The wavelength composition and temporal modulation of ambient lighting strongly affect refractive development in young tree shrews. Exp Eye Res 155:75-84
Ward, Alexander H; Siegwart, John T; Frost, Michael R et al. (2017) Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews. Vis Neurosci 34:E003
Norton, Thomas T (2016) What Do Animal Studies Tell Us about the Mechanism of Myopia-Protection by Light? Optom Vis Sci 93:1049-51
Ward, Alexander H; Siegwart Jr, John T; Frost, Michael R et al. (2016) The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews. Exp Eye Res 145:289-296
Grytz, Rafael; Siegwart Jr, John T (2015) Changing material properties of the tree shrew sclera during minus lens compensation and recovery. Invest Ophthalmol Vis Sci 56:2065-78
Guo, Lin; Frost, Michael R; Siegwart Jr, John T et al. (2014) Scleral gene expression during recovery from myopia compared with expression during myopia development in tree shrew. Mol Vis 20:1643-59
He, Li; Frost, Michael R; Siegwart Jr, John T et al. (2014) Gene expression signatures in tree shrew choroid during lens-induced myopia and recovery. Exp Eye Res 123:56-71
He, Li; Frost, Michael R; Siegwart Jr, John T et al. (2014) Gene expression signatures in tree shrew choroid in response to three myopiagenic conditions. Vision Res 102:52-63
Norton, Thomas T; Siegwart Jr, John T (2013) Light levels, refractive development, and myopia--a speculative review. Exp Eye Res 114:48-57

Showing the most recent 10 out of 32 publications