title: Effects of intravitreal injection of a Rho-GTPase inhibitor (BA-210), or CNTF combined with an analogue of cAMP, on the dendritic morphology of regenerating retinal ganglion cells.
abstract: OBJECTIVE
  In adult rats, intravitreal injections of the Rho-GTPase inhibitor C3 transferase (BA-210), or a cocktail of recombinant ciliary neurotrophic factor (CNTF) and a cyclic AMP analogue (CPTcAMP), increase retinal ganglion cell (RGC) survival and axonal regeneration. Here we examined whether these treatments also affect the dendritic architecture of regrowing RGCs.
  
  
  METHODS
  In Fischer F344 rats, one optic nerve was cut and an autologous peripheral nerve graft was sutured onto it. Rats then received intravitreal injections (4 μl) of saline, BA-210 or CNTF + CPTcAMP four and eleven days after the PN graft surgery. After 5 weeks, regenerating RGCs were retrogradely labelled with fluorogold (FG) and in living wholemounts the dendritic trees of FG labelled RGCs were visualised by intracellular injection of 2% Lucifer Yellow.
  
  
  RESULTS
  Injection of BA-210 or CNTF + CPTcAMP resulted in significantly more regenerating RGCs with abnormal dendritic morphologies, including abnormally long looping processes. Compared to saline-injected regenerating controls, RGCs in BA-210 injected eyes had significantly smaller dendritic field areas and sparser dendrites, while in CNTF + CPTcAMP injected eyes there was increased branching of more distal dendrites.
  
  
  CONCLUSIONS
  While both intraocular treatments enhance RGC axonal regrowth, they also induce significant changes in RGC dendritic morphology. It remains to be determined if such changes alter the function of the regenerating neuronal population.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Drummond
authors.affiliation: Experimental and Regenerative Neurosciences, The University of Western Australia, WA, Australia School of Animal Biology, The University of Western Australia, WA, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodger
authors.affiliation: Experimental and Regenerative Neurosciences, The University of Western Australia, WA, Australia School of Animal Biology, The University of Western Australia, WA, Australia.
authors.forename: Marissa
authors.initials: M
authors.lastname: Penrose
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.
authors.forename: Donald
authors.initials: D
authors.lastname: Robertson
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia Experimental and Regenerative Neurosciences, The University of Western Australia, WA, Australia.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
mesh_terms: D036002:ADP Ribose Transferases / Q000494:pharmacology*; D000818:Animals; D001905:Botulinum Toxins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D020221:Optic Nerve Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010525:Peripheral Nerves / Q000637:transplantation; D018373:Peripheral Nervous System Agents / Q000494:pharmacology*; D011916:Rats, Inbred F344; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D013997:Time Factors; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020934:Ciliary Neurotrophic Factor; D004791:Enzyme Inhibitors; D018373:Peripheral Nervous System Agents; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins
keywords: C3 transferase; Optic nerve injury; peripheral nerve graft; regeneration; retina