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Melissa Meyer zu Horste, Verena Prokosch-Willing, Harutyun Melkonyan, Tobias Stupp, Solon Thanos; Retinal ganglion cell differentiation triggering FGF-2 is down-regulated in experi-mental visual deprivation in newborn rats. Invest. Ophthalmol. Vis. Sci. 2014;55(13):811.
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© ARVO (1962-2015); The Authors (2016-present)
Amblyopia is a developmental disease characterized by impaired visual acuity. The underlying molecular pathomechanisms remain unclear. The present work was undertaken to examine the retinal transcripts associated with amblyopia in rats with experimentally induced unilateral amblyopia.
Surgical tarsorrhaphy was performed in the eye lids of newborn Sprague-Dawley (SD) rats prior to eye opening at postnatal day 14, with the contralateral eye serving as the corresponding control. This condition was maintained for over 2 months, after which electroretinograms (ERGs) were recorded and the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing. Retinal transcripts were studied using microarray analysis. Regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and selected proteins were studied using immunohistochemistry, immunoblots and functional tests in cell cultures.
In the eyes deprived of visual experience, we found attenuated ERGs indicating altered physiological neurotransmission. Retrograde neuroanatomical staining disclosed a significantly higher number of RGCs as well as a multilayered distribution of RGCs within the retina on the visually deprived eye, in comparison to non-deprived samples, indicating incomplete programmed cell death and incomplete post-mitotic migration to the ganglion cell layer. At the molecular level, several transcripts were either up- or down-regulated, mostly in association with retinal differentiation, indicating that postnatal differentiation of the retina requires photic stimulation. Most of the transcripts, and in particular FGF-2, could be verified at the mRNA level, while some of the proteins encoded were stainable in retinal sections and gels. When added to primary retinal cell cultures at postnatal stages, FGF-2 stimulated differentiation of ganglion cells, indicating its importance for postnatal retinal development.
These data suggest that visual experience crucially shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at both the cellular and molecular levels within the retina, including regulation of powerful differentiation factors such as FGF-2.
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