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Natecia Williams, Shannon Getz, Fazila Aseem, Curran S Sidhu, Jeffrey H Boatright, P Michael Iuvone, J M Nickerson; IRBP, Dopamine, and the Development of Early Myopia. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1355.
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Interphotoreceptor retinoid-binding protein (IRBP) is a soluble protein produced by photoreceptors and pineal cells, which binds retinoids and fatty acids (Bunt-Milam & Saari. J Cell Biol. 1983;97:703-12). IRBP knockout (KO) mice develop myopia by P10 (Wisard et al. IOVS. 2011;52:5804-11). The neurotransmitter, dopamine (DA), has been observed to regulate myopia in the retina and has a negative correlation with axial-growth (Stone et al. PNAS 1989; 86:704-6). Here, we predicted that IRBP and DA interact to regulate myopia in the IRBP KO mouse. Based on experimentally induced myopia, we hypothesized a decrease in DA activity in the IRBP KO mouse retina. To better understand the relationship between IRBP and DA, we analyzed the retinal levels of the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and number of DA cells in the IRBP KO retina.
We used HPLC to determine amounts of DA and DOPAC. Immunohistochemistry was used to count tyrosine hydroxylase (TH)+ cells observed in retinas of the IRBP KO and age-matched C57BL/6J mice.
Although the IRBP KO retina develops myopia, the amount of DA and related biomolecules were increased in the IRBP KO compared to the C57BL/6J. DOPAC levels were significantly increased by 13% at postnatal day 36(P36) (B6: 341 pg/mg ± 15 SEM; KO: 386 pg/mg ± 11 SEM. P < 0.05) and 76% at P60 (B6: 309 pg/mg ± 39 SEM; KO: 544 pg/mg ± 63 SEM. P < 0.005). DA levels in the IRBP KO followed a similar trend and were increased by 27% at P36 and 19% at P60. Also, the P36 IRBP KO retina had a 39% increase in the cells expressing TH (B6: 706 TH+ cells per retina ± 89 SD; KO: 982 TH+ cells per retina ± 127 SD. P < 0.001).
DA has multiple functions in the central nervous system, including the eye. Although previous studies have shown a decrease in DA activity in cases of myopia, our results demonstrate that myopia can develop along with elevated levels of DA. Further examination is required to understand the roles that IRBP and DA play in the development of the elongated eye in the IRBP KO. Our results suggest that developmental eye elongation before eye-opening is controlled by different mechanisms from vision-dependent experimental myopia.
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