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Regan S. Ashby, Guang Zeng, Amelia J. Leotta, Dennis Y. Tse, Sally A. McFadden; Egr-1 mRNA Expression Is a Marker for the Direction of Mammalian Ocular Growth. Invest. Ophthalmol. Vis. Sci. 2014;55(9):5911-5921. doi: https://doi.org/10.1167/iovs.13-11708.
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The immediate early gene Egr-1 is thought to form part of the pathway that mediates abnormal ocular growth. This study investigated whether the mRNA expression levels of Egr-1 in a mammalian retina are modulated differentially, depending on the direction of ocular growth.
To induce accelerated growth and myopia, guinea pigs wore a −5 diopter (D) lens over one eye from 4 to 11 days of age. To induce inhibited growth, the lens was removed after 7 days of −5 D lens wear, and the eye allowed to recover from myopia for 3 days. Ocular parameters and Egr-1 mRNA levels were subsequently assessed, and compared to untreated fellow eyes and eyes from untreated littermates. Possible circadian changes in Egr-1 mRNA levels were also determined in 18 additional animals by taking measures every 4 hours during a 24-hour cycle.
Ocular compensation to a −5 D lens occurred after 7 days (Δ −4.8 D, Δ +147 μm growth, N = 20). In 5 highly myopic eyes (Δ −7.4 D), Egr-1 mRNA levels in the retina were significantly downregulated relative to contralateral control (51%) and age-matched untreated (47%) eyes. Three days after the −5 D lens was removed, eyes had recovered from the myopia (Δ −0.5 D, relative change of +2.9 D, N = 4) and Egr-1 mRNA levels were significantly elevated relative to contralateral (212%) and untreated (234%) eyes, respectively. Normal Egr-1 mRNA expression was higher in the middle of the day than in the middle of the night. Immunolabeling showed strong Egr-1 reactivity in cell bodies in the inner nuclear and ganglion cell layers.
Egr-1 mRNA levels in a mammalian retina show a bi-directional persistent response to opposing ocular growth stimuli. This suggests retinal Egr-1 might act as a signal for the direction of ocular growth in different species.
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