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R. Schippert, M. Feldkaemper, F. Schaeffel; Axial Myopia in Egr–1 Knock–Out Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3326.
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In chick retina, the transcription factor ZENK is regulated by the amount and sign of imposed defocus. During induction of hyperopia by positive lenses it is upregulated, and during induction of myopia with negative lenses or diffusers it is reduced. We have tested whether mice develop myopia if they lack Egr–1, the mammalian homologue of ZENK. Homozygous, heterozygous and wildtype Egr–1 knock–out mice were studied from P28 to P98.
Knock–out mice, on a C57/BL6 background, were obtained from Taconic, NY, and bred in the animal facilities of the Institute. PCR was performed to verify genotypes. Axial eye growth was recorded using optical low coherence interferometry (the "ACMaster", Carl Zeiss Meditec, Jena), refractive state was measured with automated infrared photorefraction, corneal radius of curvature with infrared photokeratometry and grating acuity in an automated optomotor task.
As revealed by multi–comparison ANOVA, age, genotype and body weight all were correlated with axial eye length. Furthermore, refraction was significantly related to genotype. At 42 days of age, homozygous Egr–1 knock–out mice (n=9) had significantly longer eyes compared to heterozygous (+48.5±47.3µm, n=22) and wildtype (+59.9±56.8 µm, n=8) mice (Tukey–Kramer HSD: p<0.01). Refractive state of homozygous mice was significantly more myopic (by 3.4±2.4D, Tukey–Kramer HSD: p<0.01). These differences declined with age and had disappeared at the end of the measurement period (P98). Neither corneal radius of curvature, nor grating acuity were changed when Egr–1 was knocked–down.
In line with the initial assumption, homozygous Egr–1 knock–out mice had longer eyes and more myopic refractions than heterozygous or wildtype mice. Because corneal curvature was not changed, about 10D of myopia were expected from the differences in axial length. Since only 3.4D were observed, other optical variables in the eyes must have also changed. Nevertheless, the lack of Egr–1 was linked to axial eye elongation and myopia development, suggesting that Egr–1 could be involved in myopia development also in mammals.
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