Myopia is a major problem worldwide with the number of affected individuals estimated to be as high as 90% for some Asian countries. The prevalence of myopia in the US is on the rise, up from 25% in 1971-1972 to 41.6% in1999-2004, with some underserved ethnic groups such as Native Americans and Alaskan Eskimos being particularly susceptible. The annual cost of treatment approximates 2-3 billion dollars for the estimated 40-50 million affected individuals in the US. In addition, myopia can lead to secondary complications that cause severely reduced vision. Myopia is caused both by genetic and environmental factors. Humans are normally born hyperopic, with eyes too short for the optics. During development, visual experience regulates eye growth so that the eye stops growing when the length is optimal for the optics (emmetropia). Myopia occurs when the eye grows past the point of emmetropia, becoming too long. The long- (L) and middle- (M) wavelength-sensitive cones mediate visually guided eye growth. Preliminary data is presented suggesting that 1) rare variants of the L and M cone opsin genes underlie a severe inherited form of myopia 2) there is an association between common myopia and variants of L and M opsin genes and 3) the L to M cone ratio influences visually guided eye growth. The L and M cone opsin genes are highly variable, encoding a tremendous amount of amino acid sequence variation in the opsins, making them excellent candidates for causing common forms of myopia. The ratio of L to M cones is also highly variable across individuals, which produces variability in the response of retinal circuits to environmental stimuli, which in turn influences eye growth. The involvement of the L/M cone pigments and cone ratio in the mechanism regulating eye growth suggests that axial elongation can be controlled by modifying visual experience. In a pilot study, children wore special eyeglasses containing one experimental and one control lens for three months. Both lenses had the individual's optimal correction. The experimental lens had a color-blocking filter to remove red light, and a holographic diffuser to blur the image slightly. The control lens passed red and green light equally but ensured that both eyes were exposed to the same light intensity throughout the study. Axial length measurements were taken at two week intervals. Eyes wearing the experimental treatment lens grew significantly slower than eyes wearing the control lens (p=0.001), making this a very promising method for preventing myopia. This application addresses the stated objective in NEI's Health Disparities Strategic Plan to """"""""determine the etiology of human myopia and identify the risk factors associated with this and other refractive errors so as to prevent their occurrence or progression."""""""" Specific aim 1 will evaluate the role of cone ratio, axial length, and L and M cone opsin gene variants in the etiology of myopia.
Aim 2 will investigate the role of L: M cone ratio in the etiology of myopia by comparing ratios across ethnic groups particularly at risk for myopia.
Aim 3 will evaluate the potential of lenses that block specific wavelengths of light and introduce image blur in slowing axial elongation in myopic children.

Public Health Relevance

The prevalence of myopia in the US is on the rise, up from 25% in 1971-1972 to 41.6% in1999-2004, with some underserved ethnic groups such as Native Americans and Alaskan Eskimos being particularly susceptible. The annual cost of treatment approximates 2-3 billion dollars for the estimated 40-50 million affected individuals in the US, in addition, myopia can lead to secondary complications that severely impair vision. The major objectives of this grant are to investigate newly identified genes and environmental cues in the etiology of nearsightedness and to establish a newly identified treatment that, in a small pilot study, showed great promise as an effective, inexpensive, non-invasive, non-pharmacological means of slowing or stopping abnormal eye growth.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY021242-02
Application #
8328609
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Wiggs, Cheri
Project Start
2011-09-30
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$386,250
Indirect Cost
$136,250
Name
University of Washington
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Patterson, Emily J; Kalitzeos, Angelos; Kasilian, Melissa et al. (2018) Residual Cone Structure in Patients With X-Linked Cone Opsin Mutations. Invest Ophthalmol Vis Sci 59:4238-4248
Neitz, J; Neitz, M (2017) Evolution of the circuitry for conscious color vision in primates. Eye (Lond) 31:286-300
Greenwald, Scott H; Kuchenbecker, James A; Rowlan, Jessica S et al. (2017) Role of a Dual Splicing and Amino Acid Code in Myopia, Cone Dysfunction and Cone Dystrophy Associated with L/M Opsin Interchange Mutations. Transl Vis Sci Technol 6:2
Cartoni, Romain; Pekkurnaz, Gulcin; Wang, Chen et al. (2017) A high mitochondrial transport rate characterizes CNS neurons with high axonal regeneration capacity. PLoS One 12:e0184672
Patterson, Emily J; Wilk, Melissa; Langlo, Christopher S et al. (2016) Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency. Invest Ophthalmol Vis Sci 57:3853-63
Schmidt, Brian P; Touch, Phanith; Neitz, Maureen et al. (2016) Circuitry to explain how the relative number of L and M cones shapes color experience. J Vis 16:18
Davidoff, Candice; Neitz, Maureen; Neitz, Jay (2016) Genetic Testing as a New Standard for Clinical Diagnosis of Color Vision Deficiencies. Transl Vis Sci Technol 5:2
Cartoni, Romain; Norsworthy, Michael W; Bei, Fengfeng et al. (2016) The Mammalian-Specific Protein Armcx1 Regulates Mitochondrial Transport during Axon Regeneration. Neuron 92:1294-1307
Nawabi, Homaira; Belin, Stephane; Cartoni, Romain et al. (2015) Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Neuron 88:704-19
Smith 3rd, Earl L; Hung, Li-Fang; Arumugam, Baskar et al. (2015) Effects of Long-Wavelength Lighting on Refractive Development in Infant Rhesus Monkeys. Invest Ophthalmol Vis Sci 56:6490-500

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