Myopia (nearsightedness) is on the rise around the world and in the United States. It affects tens of millions of Americans and, in progressive forms, is a leading cause of blindness. Earlier research with humans and experimental animal models has made it clear that the postnatal development of the eye and refractive state involves a combination of genetic and visual factors. The rise in incidence of human myopia has been associated with increases in literacy and levels of education, although the nature of the relationship is unclear. Research using animal models has established that visual stimuli related to retinal defocus regulate eye growth and refractive state. The studies described in this proposal use various visual manipulations to explore the temporal integration of visual stimuli that affect eye growth and the biochemical mechanisms that may underlie these changes. The following questions are asked: (1) How does the eye temporally integrate different visual stimuli for the regulation of eye growth? To answer this, the investigators will contrast the effects of different states of defocus or deprivation with corrected or clear vision and examine the stimulus durations necessary to elicit different ocular growth responses. (2) Do ocular circadian rhythms in IOP, axial length and choroid thickness play a role in the regulation of ocular growth? Specifically, the investigators will examine the phase relationships between these different rhythms during induced changes in ocular growth rate. (3) How do the temporal pattern and accuracy of accommodation affect the degree of blur experienced during near work tasks and when viewing through negative power spectacle lenses? These measures of accommodative behavior will then be correlated with the degree of experimental myopia induced. (4) What are the changes in scleral extracellular matrix during experimentally induced changes in ocular growth, and how are they controlled? Using ocular tissues from the other experiments, the investigators will quantify changes in scleral extracellular components and correlate them with visually induced increases and decreases in ocular growth rate. In addition, the possibility that retinoic acid synthesis by the choroids/RPE plays a role in the signal cascade from retina to sclera will be explored. This project will bring together several lines of investigation to help answer important questions relating to how myopia develops in response to altered visual experience. These studies will provide new information for understanding the association of near work, such as reading, and the development of myopia in humans.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences B Study Section (VISB)
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Oberdorfer, Michael
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New England College of Optometry
Other Basic Sciences
Schools of Optometry/Ophthalmol
United States
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Benavente-PĂ©rez, Alexandra; Nour, Ann; Troilo, David (2014) Axial eye growth and refractive error development can be modified by exposing the peripheral retina to relative myopic or hyperopic defocus. Invest Ophthalmol Vis Sci 55:6765-73
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
Benavente-Perez, Alexandra; Nour, Ann; Troilo, David (2012) The effect of simultaneous negative and positive defocus on eye growth and development of refractive state in marmosets. Invest Ophthalmol Vis Sci 53:6479-87
Coletta, Nancy J; Marcos, Susana; Troilo, David (2010) Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects of age and refractive error. Vision Res 50:2515-29
Ivanova, Elena; Hwang, Grace-Soon; Pan, Zhuo-Hua et al. (2010) Evaluation of AAV-mediated expression of Chop2-GFP in the marmoset retina. Invest Ophthalmol Vis Sci 51:5288-96
Hendrickson, Anita; Troilo, David; Djajadi, Hidayat et al. (2009) Expression of synaptic and phototransduction markers during photoreceptor development in the marmoset monkey Callithrix jacchus. J Comp Neurol 512:218-31
Troilo, David; Totonelly, Kristen; Harb, Elise (2009) Imposed anisometropia, accommodation, and regulation of refractive state. Optom Vis Sci 86:E31-9
Shelton, Lilian; Troilo, David; Lerner, Megan R et al. (2008) Microarray analysis of choroid/RPE gene expression in marmoset eyes undergoing changes in ocular growth and refraction. Mol Vis 14:1465-79
Troilo, David; Quinn, Nicole; Baker, Kayla (2007) Accommodation and induced myopia in marmosets. Vision Res 47:1228-44
Troilo, David; Nickla, Debora L; Mertz, James R et al. (2006) Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets. Invest Ophthalmol Vis Sci 47:1768-77

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