title: Rescuing axons from degeneration does not affect retinal ganglion cell death.
abstract: After a traumatic injury to the central nervous system, the distal stumps of axons undergo Wallerian degeneration (WD), an event that comprises cytoskeleton and myelin breakdown, astrocytic gliosis, and overexpression of proteins that inhibit axonal regrowth. By contrast, injured neuronal cell bodies show features characteristic of attempts to initiate the regenerative process of elongating their axons. The main molecular event that leads to WD is an increase in the intracellular calcium concentration, which activates calpains, calcium-dependent proteases that degrade cytoskeleton proteins. The aim of our study was to investigate whether preventing axonal degeneration would impact the survival of retinal ganglion cells (RGCs) after crushing the optic nerve. We observed that male Wistar rats (weighing 200-400 g; n=18) treated with an exogenous calpain inhibitor (20 mM) administered via direct application of the inhibitor embedded within the copolymer resin Evlax immediately following optic nerve crush showed a delay in the onset of WD. This delayed onset was characterized by a decrease in the number of degenerated fibers (P<0.05) and an increase in the number of preserved fibers (P<0.05) 4 days after injury. Additionally, most preserved fibers showed a normal G-ratio. These results indicated that calpain inhibition prevented the degeneration of optic nerve fibers, rescuing axons from the process of axonal degeneration. However, analysis of retinal ganglion cell survival demonstrated no difference between the calpain inhibitor- and vehicle-treated groups, suggesting that although the calpain inhibitor prevented axonal degeneration, it had no effect on RGC survival after optic nerve damage.
authors.affiliation: Laboratório de Neurobiologia da Retina, Centro de Ciências da Saúde, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, Brasil.
authors.forename: S
authors.initials: S
authors.lastname: de Lima
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: B S
authors.initials: BS
authors.lastname: Mietto
authors.affiliation: Laboratório de Neurobiologia da Retina, Centro de Ciências da Saúde, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, Brasil.
authors.forename: C
authors.initials: C
authors.lastname: Paula
authors.affiliation: Laboratório de Neurobiologia da Retina, Centro de Ciências da Saúde, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, Brasil.
authors.forename: T
authors.initials: T
authors.lastname: Muniz
authors.affiliation: Laboratório de Neurodegeneração e Reparo, Departamento de Patologia, Faculdade de Medicina, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.
authors.forename: A M B
authors.initials: AM
authors.lastname: Martinez
authors.affiliation: Laboratório de Neurobiologia da Retina, Centro de Ciências da Saúde, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, Brasil.
authors.forename: P F
authors.initials: PF
authors.lastname: Gardino
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D046529:Microscopy, Electron, Transmission; D009409:Nerve Crush; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D011145:Polyvinyls / Q000494:pharmacology*; D017208:Rats, Wistar; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D014855:Wallerian Degeneration / Q000188:drug therapy* / Q000473:pathology
chemical_list: D006023:Glycoproteins; D011145:Polyvinyls; C039304:calpain inhibitors; C016438:ethylenevinylacetate copolymer