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M. A. Scott, A. J. Fischer; Sonic Hedgehog in Normal and Acutely Damaged Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):626.
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In mature retina Müller glia have been shown to express Patched, the receptor for Sonic Hedgehog (Shh). Goals of this study were to test whether the inhibition of Shh signaling influences Müller glia in normal or acutely damaged chicken retinas.
Postnatal chickens were injected intraocularly with a sterile saline solution of3-keto-N-aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine (KAAD-cyclopamine) in 25% dimethyl sulfoxide (DMSO), and/or N-methyl D-aspartate (NMDA). Eyes were injected with KAAD-cyclopamine either before or after NMDA-injection. We used standard methods of immunocytochemistry on frozen sections of retinas to assay for proliferation (labeling for BrdU), gliosis (immunolabeling for glial fibrillary acid protein[GFAP]), or cell death (labeling for fragmented DNA and immunoreactivity for cleaved-caspase3).
Inhibition of Shh-signaling in normal retinas results in acute gliosis, indicated by up-regulation of GFAP. Retinas treated with KAAD-cyclopamine before NMDA-treatment had significantly fewer dying cells that were TUNEL-positive cells. Conversely, retinas treated with KAAD-cyclopamine after treatment with NMDA contained fewer proliferating cells and showed an increase in the number of apoptotic cells in both the outer nuclear and ganglion cell layers. These apoptotic cells were TUNEL-positive and immunoreactive for cleaved-caspase 3
Shh-signaling may normally keep Müller glia quiescent and non-reactive. Antagonism of Shh signaling in normal retinas causes Müller glia to become reactive and, in turn, neuroprotective against severe excitotoxic insult. Shh-signaling in acutely damaged retinas may influence Müller glia-derived progenitors, ganglion cells, and photoreceptors. We propose that shh-signaling plays distinctly different roles in normal and damaged retinas.
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