Rescuing axons from degeneration does not affect retinal ganglion cell death

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.

Dexamethasone and methylprednisolone in treatment of indirect traumatic optic neuropathy.

A randomized, double blind study was carried out to compare the efficacy of dexamethasone and methylprednisolone in the treatment of indirect traumatic optic neuropathy. Twenty-one patients, 20 male and 1 female, were diagnosed as having suffered from indirect traumatic optic neuropathy. The time from injury to treatment was within 7 days. The average age was 26.38 +/- 11.89 years. The most common cause of injury was motor vehicle accident (MVA). Associated head and maxillofacial injury were reported 43.48 and 34.78 per cent, respectively. Before treatment, no light perception was detected in 19.05 per cent of the participants. Treatments were randomized: ten patients received dexamethasone intravenously for 72 hours and 11 methylprednisolone. The best corrected visual acuities (BCVA) were determined using the Snellen Chart before and 1, 2, 3, 7, 14 and 60 days after treatment. Three or more lines of improvement of the BCVA, were found in 70 and 67 per cent of patients treated with dexamethasone, and 45.45 and 33.33 per cent of patients treated with methylprednisolone, at 2 weeks and 2 months, respectively. There were no significant differences in age, cause of injury, injury to treatment interval, initial BCVA and visual improvement between the two groups.