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Shanu Markand, Micah A Chrenek, Priyanka Priyadarshani, Jeffrey H Boatright, J M Nickerson; Upregulation of myopia-related genes in the Interphotoreceptor retinoid-binding protein (IRBP) knockout (KO) mouse model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2054.
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© ARVO (1962-2015); The Authors (2016-present)
Untreated myopia, a refractive error disorder is the most common cause of visual impairment worldwide and is associated with heavy economic burden. Mechanisms underlying myopia are not yet clear. One of the primary focuses of our laboratory is to understand the role of IRBP in normal eye development. IRBP is a major protein of the sub-retinal space and plays a crucial role in the visual cycle. Mutations in human RPB3 (IRBP) gene are associated with high myopia and retinal dystrophy. We previously reported eye size defects, (Post-natal day, P8), profound myopia and retinal degeneration (RD), at P23 in the IRBP KO mice. The purpose of this study was to test the hypothesis that several genes implicated in myopia are upregulated in the retinas of IRBP KO mice at P5, an age preceding myopia in IRBP KO mice and at P213, post RD.
Retinal cDNA from C57BL/6J (WT) and congenic IRBP KO mice at P5 (WT, n=8; KO, n=5) and P213 (WT, n=8; KO, n=6) were subjected to digital droplet PCR. A total of 28 genes associated with myopia were selected. HPRT was used as a housekeeping gene. Ratio (target/HPRT), standard error of the mean (SEM) were recorded. An unpaired t-test with Welch's correction assuming unequal variances was used to assess statistical significance. A p value <0.05 was considered significant.
Data analysis revealed upregulation in several genes in IRBP KO mice. Interestingly, most of the altered genes at P5 were not significantly different at P213 and vice versa. At P5, Aplp2, Calb1, Gjd2, Isl1, Sntb1 (p<0.01); Vsx2, Ripk2 and Egr1 (p<0.05) were upregulated while Tox (p<0.01) was downregulated. At P213, C1q, Grm6, Isl1 and Otx2 (p<0.01); Calb2, Sntb1and Zeb2 (p<0.05); Vsx2 and Tox (p<0.001) were upregulated.
Our data support the hypothesis that several of myopia-genes are upregulated in IRBP KO retinas indicating the importance of IRBP in early eye size determination and in myopia pathogenesis. Our results highlight the importance of Aplp2, Sntb1, Isl1, Tox and Vsx2 signaling pathways and suggest targets to treat IRBP mediated myopia and RP. This may suggest genetic mechanisms in the predilection to increased axial length before vision or light mediated signaling.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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