In the United States, myopia affects nearly 25 percent of the population, while in certain other developed countries the proportion of the population affected increases to 80 percent or more. Pathological myopia is also a leading cause of blindness. Therefore, understanding the mechanisms underlying the regulation of ocular growth is critical towards understanding how and why it goes awry in eyes that develop ametropias, and might lead to the development of new therapies. ? ? Recent work has indicated that changes in the rate of ocular growth are associated with alterations in ocular circadian rhythms. The work proposed here seeks to extend these original observations, to better understand the mechanisms underlying these effects. Specifically, we ask whether the phase shifts in the rhythms in axial length and choroid thickness (two ocular circadian rhythms the phases of which have been shown to be altered by visual manipulations that alter growth rate) are temporally correlated with visually induced changes in rate of ocular growth. This would imply that the changes in thickness of the choroid might play a causal role in ocular growth regulation. To further explore this notion we will test the hypothesis that daily transient changes in choroidal thickness are part of the signal pathway mediating emmetropization. Specifically, we ask whether the visual signals mediating changes in choroidal thickness and those mediating changes in ocular growth rate are the same, or are separate. Finally, we will look at some visual and chemical effects on the circadian rhythm in scleral proteoglycan synthesis to further explore how the phases of these ocular rhythms might interact in regulating ocular growth. We will also test the hypothesis that there is a diurnal rhythm in choroidal retinoic acid synthesis that might influence the diurnal rhythm in scieral proteoglycan synthesis. The results from these three Aims will bring us closer to understanding the molecular mechanisms underlying ocular growth regulation, and elucidate the influence of the choroid in these mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013636-02
Application #
6616827
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Oberdorfer, Michael
Project Start
2002-08-01
Project End
2006-05-31
Budget Start
2003-06-01
Budget End
2004-05-31
Support Year
2
Fiscal Year
2003
Total Cost
$184,771
Indirect Cost
Name
New England College of Optometry
Department
Other Basic Sciences
Type
Schools of Optometry/Ophthalmol
DUNS #
076614874
City
Boston
State
MA
Country
United States
Zip Code
02115
Chakraborty, Ranjay; Ostrin, Lisa A; Nickla, Debora L et al. (2018) Circadian rhythms, refractive development, and myopia. Ophthalmic Physiol Opt 38:217-245
Nickla, Debora L; Jordan, Kelsey; Yang, Jane et al. (2017) Brief hyperopic defocus or form deprivation have varying effects on eye growth and ocular rhythms depending on the time-of-day of exposure. Exp Eye Res 161:132-142
Nickla, Debora L; Thai, Pearl; Zanzerkia Trahan, Rinita et al. (2017) Myopic defocus in the evening is more effective at inhibiting eye growth than defocus in the morning: Effects on rhythms in axial length and choroid thickness in chicks. Exp Eye Res 154:104-115
Nickla, Debora L; Totonelly, Kristen (2016) Brief light exposure at night disrupts the circadian rhythms in eye growth and choroidal thickness in chicks. Exp Eye Res 146:189-95
Nickla, Debora L; Totonelly, Kristen (2015) Choroidal thickness predicts ocular growth in normal chicks but not in eyes with experimentally altered growth. Clin Exp Optom 98:564-70
Nickla, Debora L; Yusupova, Yekaterina; Totonelly, Kristen (2015) The Muscarinic Antagonist MT3 Distinguishes Between Form Deprivation- and Negative Lens-Induced Myopia in Chicks. Curr Eye Res 40:962-7
Nickla, Debora L; Lee, Laimeng; Totonelly, Kristen (2013) Nitric oxide synthase inhibitors prevent the growth-inhibiting effects of quinpirole. Optom Vis Sci 90:1167-75
Morgan, Ian G; Ashby, Regan S; Nickla, Debora L (2013) Form deprivation and lens-induced myopia: are they different? Ophthalmic Physiol Opt 33:355-61
Nickla, Debora L (2013) Ocular diurnal rhythms and eye growth regulation: where we are 50 years after Lauber. Exp Eye Res 114:25-34
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

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