|
 |
 |
|
Secondary Degeneration In The Optic Nerve And Potential Therapies 1. Sarah Dunlop¹ ¹School of Animal Biology, The University of Western Australia, Crawley, Australia Purpose: To characterize cellular events during secondary degeneration following partial optic nerve injury in rat and examine potential neuroprotective therapies. Methods: Animals received a partial injury to the dorsal optic nerve leaving ventral optic axons and parent retinal ganglion cell somata intact but vulnerable to secondary degeneration. We examined the effects of acute treatment with near infrared light and chronic treatment with the calcium channel blocker lomerizine dihydrochloride. Visual function was assessed behaviourally and tissue vulnerable to secondary degeneration analysed immunohistochemically and ultrastructurally. Results: Visual function declines by 8 days and remains poor long term. In the optic nerve, oxidative stress occurs rapidly (5 minutes) and spreads via the astrocytic network and to the retina. Retinal ganglion cell death is apparent at 2 weeks with a halving of cell density by 1 month which is mirrored by a decreased density of myelinated axons. Optic axons also undergo chronic changes by 3 months including swelling and myelin sheath abnormalities. Acute near infrared light reduces oxidative stress and restores visual function at 8 days. Lomerizine hydrochloride prevents secondary retinal ganglion cell death such that values do not differ from normal at 1 month; however lomerizine hydrochloride does not prevent the decline in myelinated axon density and only partially restores vision. Conclusions: Secondary degeneration involves sequential cellular events some of which can ameliorated by acute near infrared light and others by chronic lomerizine hydrochloride. Our findings suggest that combinatorial therapies will be required to prevent secondary degeneration and maintain vision. |
 |