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Z. Zhang, S. Geller, J. Su, J. G. Flannery, C. F. Wildsoet; Effect of Imposed Defocus on the Profile of Gene Expression in Chick Retinal Pigment Epithelium. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4417.
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To elucidate the effect of imposed defocus on the profile of gene expression in chicken retinal pigment epithelium (RPE) using DNA microarray analysis and real-time PCR.
White Leghorn chicks wore monocular positive or negative lenses (+10 D & -10 D) from age 19 days for 2 or 48 hours; fellow eyes were untreated. Choroidal thickness responses were measured using high frequency A-scan ultrasonography (n=32). Total RNA was extracted from isolated RPE and used for DNA microarray (n=3) and real-time PCR (n=16) studies. The former used only 48 hr samples and an Affymetrix GeneChip, and data were analyzed using GeneSifter software.
Out of a possible maximum of 38535 genes detectible with the Affymetrix Chicken Genome chip, 13389 were expressed in RPE from -10 D lens-treated eyes compared to 15881 genes for fellow (control) eyes, and of these, 1582 were exclusive to RPE from control eyes and 431 were exclusive to RPE from eyes wearing -10D lens (n=3, p<0.05). Among the 9992 genes expressed in RPE from both -10D lens-treated and fellow eyes, 157 genes were up-regulated by more than 3 fold and 632 were down-regulated by more than 3 folds in treated compared to fellow eyes. Among the down-regulated genes were TGF-beta3, SMAD2 and SMAD3 (X 2.1, 1.9 and 1.5 fold, respectively). Among the up-regulated genes were TGF-beta receptor1, TGF-beta receptor3, somatostatin, insulin receptor substrate and insulin-like growth factor binding protein (X 2.7, 2.8, 2.1, 2, 2.1 fold, respectively). Real-time PCR analyses revealed up-regulation of somatostatin receptor2 and IGF1R in RPE from -10D lens treated eyes, and down-regulation in RPE from +10D lens-treated eyes at both time points (p<0.05 in all cases). These changes were coupled to significant decreases and increases in choroidal thickness respectively (p<0.01, 2 & 48 hr).
Imposed defocus results in significant differences in RPE gene expression profiles that also may show sign-dependent differences. These findings offer a mechanism by which the RPE could encode bidirectional retina-derived growth regulatory signals that are assumed to modulate the growth of the choroid and sclera in young eyes. They also provide new directions for research into myopia control therapy.
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