July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The association between L:M cone ratio, cone opsin genes and myopia susceptibility
Author Affiliations & Notes
  • Lene A. Hagen
    National Centre for Optics, Vision and Eye Care, University of South-Eastern Norway, Kongsberg, Norway
  • Solveig Arnegard
    National Centre for Optics, Vision and Eye Care, University of South-Eastern Norway, Kongsberg, Norway
  • James A Kuchenbecker
    Department of Ophthalmology, University of Washington Medical School, Washington, United States
  • Stuart J. Gilson
    National Centre for Optics, Vision and Eye Care, University of South-Eastern Norway, Kongsberg, Norway
  • Maureen Neitz
    Department of Ophthalmology, University of Washington Medical School, Washington, United States
  • Jay Neitz
    Department of Ophthalmology, University of Washington Medical School, Washington, United States
  • Rigmor C Baraas
    National Centre for Optics, Vision and Eye Care, University of South-Eastern Norway, Kongsberg, Norway
  • Footnotes
    Commercial Relationships   Lene Hagen, None; Solveig Arnegard, None; James Kuchenbecker, None; Stuart Gilson, None; Maureen Neitz, None; Jay Neitz, None; Rigmor Baraas, None
  • Footnotes
    Support  Norwegian Ministry of Education and Research, NEI R01EY028118, PHS P30 EY01730, and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4266. doi:
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      Lene A. Hagen, Solveig Arnegard, James A Kuchenbecker, Stuart J. Gilson, Maureen Neitz, Jay Neitz, Rigmor C Baraas; The association between L:M cone ratio, cone opsin genes and myopia susceptibility. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4266.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Cone function contributes to myopia susceptibility by modulating contrast signals that indicate how well images are focused on the retina. Myopia susceptibility is associated with interchange haplotypes of the L and M opsin genes that reduce the amounts of photopigment in the cones that express them. This susceptibility is modulated by L:M cone ratio. The purpose of this study was to examine L:M cone ratios, L and M cone opsin genes and their association with refractive error in Norwegian adolescents, a population with low myopia prevalence.

Methods : One hundred and thirty-six genetically confirmed normal trichromats (16–19 yrs; 60 males) were included. All were healthy Norwegian Caucasians with normal habitual visual acuity and stereo acuity. Cycloplegic autorefraction and ocular biometry were obtained. DNA was extracted from saliva, and L and M cone opsin genes were sequenced. Spectral sensitivity functions were measured with ERG, and L:M cone ratios were estimated after adjustment for individual cone opsin genetics.

Results : Myopia prevalence (≤ -0.50D) was 8% in males and 20% in females. Mean %L cones was 80% in males and 84% in females, which is higher than what has been reported in males in other populations. Females with low %L cones were more myopic than females with high %L cones (n= 39 vs. 37; -0.03D vs. 0.58D; p= 0.01). The myopia prevalence was the same in females who were homozygous for the L opsin exon 3 haplotype (n= 22) as in the males (n= 60; 9% and 8% respectively), but much higher in females who were heterozygous for the L opsin exon 3 haplotype (n= 54; 24% myopia).

Conclusions : In syndromic forms of myopia caused by L/M interchange mutations, it has been proposed that one submosaic of cones with normal levels of opsin expression and a second submosaic with low expression produce spurious contrast signals which make the eye susceptible to accelerated growth. Individuals with highly skewed cone ratios are protected from these effects, perhaps partly explaining the low rate of myopia in Norwegians. The higher incidence of myopia in females could be explained if milder versions of the opsin mutations play a role in juvenile onset myopia, since females are twice as likely to have a mutant allele carried on the X-chromosome. In addition, heterozygous females are more likely to have two cone submosaics with different levels of opsin expression increasing their susceptibility to myopia.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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