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Regan S. Ashby, Guang Zeng, Amelia Leotta, Sally A. McFadden, V; Changes in Egr-1 Expression in the Guinea Pig Retina in Response to Negative Lens-wear. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3925.
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In chicks, alterations in the retinal mRNA expression of the immediate early gene Egr-1 is amongst the earliest known molecular changes observed in response to optically induced modulation of eye growth. This study investigated whether alterations in retinal Egr-1 mRNA levels are also observed in a mammalian model (guinea pig) in response to longer-term exposure to minus lens-wear, and recovery from such lens-wear.
Four day-old guinea pigs were treated for 6 days with -5D lenses, before retinal tissue was collected. For recovery experiments, retinal tissue was collected following 3 days of lens removal. Changes in Egr-1 mRNA levels were determined by RT-PCR. Primers were designed through sequence alignment of the human, mouse and rat (closest phylogenetic relative) Egr-1 gene. Product specificity was validated through melt curve analysis, gel electrophoresis and automated sequencing. For immunolabelling, tissue was fixed in 4% paraformaldehyde for 1hr, and primary labelled overnight.
Following 6 days of -5D lens-wear (difference; -7.4D), Egr-1 mRNA levels in the retina were significantly down-regulated (~2 fold) in comparison to contralateral control or age-matched untreated values. In contrast, following 3 days of recovery from -5D lenses (difference; -0.5D) retinal Egr-1 mRNA levels were significantly elevated (~2-fold) compared to contralateral control or age-matched untreated values. Preliminary immunolabelling data suggest that Egr-1 is expressed in a specific subset of ganglion and amacrine cells, and also in the synaptic terminals of bipolar cells.
As observed in chicks, Egr-1 mRNA levels in a mammalian retina show a bi-directional response to opposing growth stimuli, with mRNA levels down-regulated in response to negative lens-wear (growth stimulating) and up-regulated in response to recovery from negative lens-wear (growth suppressing). Changes in Egr-1 mRNA levels in response to longer periods of optical defocus may therefore be a general signal for the direction of ocular growth in all species.
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