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.
Subject(s)
Animals , Male , Polyvinyls/pharmacology , Retinal Ganglion Cells/drug effects , Axons/drug effects , Wallerian Degeneration/drug therapy , Glycoproteins/pharmacology , Optic Nerve Injuries/drug therapy , Axons/pathology , Immunohistochemistry , Cell Survival/drug effects , Treatment Outcome , Cell Death/drug effects , Cell Death/physiology , Rats, Wistar , Optic Nerve Injuries/pathology , Microscopy, Electron, Transmission , Nerve CrushABSTRACT
In this study we characterize the presence of muscarinic acetylcholine receptors (mAChR) in the isthmo-optic nucleus (ION) of chicks by immunohistochemistry with the M35 antibody. Some M35-immunoreactive fibers were observed emerging from the retinal optic nerve insertion, suggesting that they could be centrifugal fibers. Indeed, intraocular injections of cholera toxin B (CTb), a retrograde tracer, and double-labeling with M35 and CTb in the ION confirmed this hypothesis. The presence of M35-immunoreactive cells and the possible mAChR expression in ION and ectopic neuron cells in the chick brain strongly suggest the existence of such a cholinergic system in this nucleus and that acetylcholine release from amacrine cells may mediate interactions between retinal cells and ION terminals
Subject(s)
Animals , Chickens , Optic Nerve/cytology , Receptors, Muscarinic/analysis , Retina/cytology , Antibodies, Monoclonal/analysis , Immunochemistry , Nerve Fibers/chemistry , Optic Nerve/chemistry , Rabbits , Receptors, Muscarinic/immunology , Retina/chemistryABSTRACT
1. The correlation between neurotransmitter substances in specific cell types has renewed interest in the morphology of amacrine cells. In this paper we describe the morphology of two types of amacrine cells in Golgi-stained chick retinas. 2. The first cell type was classified as an asymmetric bistratified amacrine cell suggested to play a role in the formation of complex ganglion cell receptive fields. 3. The second was classified as a bistratified amacrine cell. Their processes were stratified at sublayers 1 and 4 of the inner plexiform layer and their morphological features were similar to those of dopaminergic cells in the chick retina.