title: Target-derived neurotrophins may influence the survival of adult retinal ganglion cells when local neurotrophic support is disrupted: Implications for glaucoma.
abstract: Following target innervation, developing and neonatal retinal ganglion cells (RGCs) depend on neurotrophic factors from their target tissue for survival. This dependence is reduced for adult RGCs which rely primarily on trophic support from their local environment; however, some findings indicate that target tissue may play a role in the long-term survival of RGCs. We propose that a deficiency in neurotrophic factors from the target tissue may influence the survival of RGCs when local neurotrophic support is disrupted. Furthermore, we propose that this hypothesis may explain, at least in part, the progressive loss of RGCs in optic neuropathies such as glaucoma. Neurotrophic factors are present in the adult superior colliculus and they are trafficked to the retina; however, removal or lesioning of the adult target tissue results in little or no RGC loss for up to several months. In vitro, adult RGCs will survive when maintained by co-culturing these neurons with their target tissue. As well, the timing and pattern of adult RGC loss is consistent with that seen in glaucoma and in reports of delayed RGC loss following target-removal. Our hypothesis can be tested by selectively disrupting local neurotrophic support and evaluating RGC survival when target-derived neurotrophic support is maintained and when it is disrupted. Specifically, intravitreal injection of blocking antibodies could be used to disrupt local neurotrophic signaling, while aspiration of the superior colliculus will eliminate retrograde transport from the primary target tissue in rodents. The results of these experiments would provide valuable information concerning the influence of target-derived neurotrophic support when local neurotrophin signaling is disrupted. Specifically, this research could verify whether deficiencies in target-derived neurotrophic support play a role in RGC loss during glaucoma. A further understanding of this mechanism may lead to the development of effective neuroprotective strategies for treating glaucoma.
authors.affiliation: Neuron Survival and Regeneration Laboratory, Department of Anatomy and Neurobiology, Dalhousie University, 5850 College Street, Halifax, NS, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Murphy
authors.forename: D B
authors.initials: DB
authors.lastname: Clarke
mesh_terms: D000328:Adult; D002470:Cell Survival; D005901:Glaucoma / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008954:Models, Biological; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000502:physiology*; D012307:Risk Factors
chemical_list: D009414:Nerve Growth Factors