This project seeks to contribute to the understanding of the etiology of myopia, a leading cause of blindness, by studying the severe myopia produced by deprivation of form vision in chickens. This animal model has three important features: the visual deprivation of one part of the retina produces myopia of only that part of the eye, and the scleral growth can be modulated up or down as necessary to compensate for myopia or hyperopia, suggesting that the eye can sense its refractive error and compensate for it. This has important implications in understanding how the eye grows and how it can go awry in clinical myopia.Three sets of experiments are proposed: (i) To study the cellular basis of myopia and emmetropization, the bidirectional modulation of scleral growth will be investigated in an in vitro system as assessed by incorporation of radiolabeled sulfur into in organ cultures and in dissociated cell cultures. The increase in proteoglycan synthesis in myopic scleras and cells of myopic eyes, and the decrease in those of recovering eyes will be studied to determine whether the modulation is achieved via a growth factor continuously or transiently released. Conditioned medium experiments will investigate the experiments will investigate the roles of he retinal pigment epithelium, choroid and retina as sources of relevant growth factors. Finally, different known growth factors will be added to the cultures to determine their effect on scleral growth in vitro. (ii) By in vivo studies, evidence will be sought that the recognized role of dopamine in the amelioration in form deprivation myopia represents a specific inhibition of the deprivation effect by using agonists on partially occluded eyes.In addition, scleras of tree shrews, which provide a mammalian model for myopia, will be studied to determine whether the myopia in these animals is also largely due to enhanced growth of the posterior sclera. (iii) The nature of the emmetropization process will be explored with experiments directed at determining the roles of the choroid and sclera in compensating for myopia or hyperopia.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37EY002727-20
Application #
2684470
Study Section
Special Emphasis Panel (NSS)
Project Start
1978-12-01
Project End
2002-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
20
Fiscal Year
1998
Total Cost
Indirect Cost
Name
City College of New York
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
603503991
City
New York
State
NY
Country
United States
Zip Code
10031
Zhu, Xiaoying; McBrien, Neville A; Smith 3rd, Earl L et al. (2013) Eyes in various species can shorten to compensate for myopic defocus. Invest Ophthalmol Vis Sci 54:2634-44
Zhu, Xiaoying (2013) Temporal integration of visual signals in lens compensation (a review). Exp Eye Res 114:69-76
Sheng, Caren; Zhu, Xiaoying; Wallman, Josh (2013) In vitro effects of insulin and RPE on choroidal and scleral components of eye growth in chicks. Exp Eye Res 116:439-48
Nickla, Debora L; Zhu, Xiaoying; Wallman, Josh (2013) Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning. Ophthalmic Physiol Opt 33:245-56
Rucker, Frances J; Wallman, Josh (2012) Chicks use changes in luminance and chromatic contrast as indicators of the sign of defocus. J Vis 12:
Nickla, Debora L; Wallman, Josh (2010) The multifunctional choroid. Prog Retin Eye Res 29:144-68
Zhu, Xiaoying; Wallman, Josh (2009) Temporal properties of compensation for positive and negative spectacle lenses in chicks. Invest Ophthalmol Vis Sci 50:37-46
Zhu, Xiaoying; Wallman, Josh (2009) Opposite effects of glucagon and insulin on compensation for spectacle lenses in chicks. Invest Ophthalmol Vis Sci 50:24-36
Rucker, Frances J; Wallman, Josh (2009) Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus: evidence that the eye uses longitudinal chromatic aberration to guide eye-growth. Vision Res 49:1775-83
Kee, Chea-Su; Hung, Li-Fang; Qiao-Grider, Ying et al. (2007) Temporal constraints on experimental emmetropization in infant monkeys. Invest Ophthalmol Vis Sci 48:957-62

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