Endocrine Abstracts (2011) 26 P228

Non-traditional effects of GH: a survival factor for retinal ganglion cells

S Harvey, W Lin, E Parker & E Sanders

University of Alberta, Edmonton, Canada.

Introduction: GH and its receptor (GHR) are expressed in retinal ganglion cells (RGCs) in the eyes of chick embryos, and in mouse, rat and human eyes. Within the retina, exogenous GH has neuroprotective actions, mediated by caspase-dependent and caspase-independent mechanisms that may also be dependent upon IGF1 signaling. Conversely, the immunoneutralization of endogenous GH promotes apoptosis in the retina and in isolated RCGs. The functional relevance of retinal GH was further assessed in the present study, by determining the effects of retinal GH knockdown on cell survival in the retinas of developing chick embryos.

Methods: At embryonic day (ED) 4 of the 21 days incubation period, a specific GH siRNA or a non-silencing siRNA was intra-vitreally injected in100 pl into the right optic cup. Eyes were removed 24 h afterwards and examined for TUNEL-labelled apoptotic cells or for GH mRNA and IGF1 mRNA content, using real-time PCR.

Results: The intra-vitreal injection of the GH siRNA lowered the retinal GH mRNA content and IGF1 mRNA content by ~50% within 24 h of injection. The withdrawal of retinal GH was accompanied by increased (P<0.01) apoptosis, particularly in clusters of retinal cells close to the optic fissure.

Conclusions: These results demonstrate that retinal GH has functional significance and it directly or indirectly (through IGF1) promotes cell survival in the developing chick neural retina. Retinal GH therefore has hitherto unknown autocrine or paracrine neuroprotective roles in retinal function.

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