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Abstract #8878 Published in IGR 5-2

A model to study differences between primary and secondary degeneration of retinal ganglion cells in rats by partial optic nerve transection

Levkovitch-Verbin H; Quigley HA; Martin KRG; Zack DJ; Pease ME; Valenta DF
Investigative Ophthalmology and Visual Science 2003; 44: 3388-3393


PURPOSE: To use a rat model of optic nerve injury to differentiate primary and secondary retinal ganglion cell (RGC) injury. METHODS: Under general anesthesia, a modified diamond knife was used to transect the superior one-third of the orbital optic nerve in albino Wistar rats. The number of surviving RGC was quantified by counting both the number of cells retrogradely filled with fluorescent gold dye injected into the superior colliculus one week before nerve injury and the number of axons in optic nerve cross sections. RGCs were counted in 56 rats, with 24 regions examined in each retinal wholemount. Rats were studied at four and eight days, and four and nine weeks after transection. The interocular difference in RGCs was also compared in five control rats that underwent no surgery and in five rats who underwent a unilateral sham operation. It was confirmed histologically that only the upper optic nerve had been directly injured. RESULTS: At four and eight days after injury, superior RGCs showed a mean difference from their fellow eyes of -30.3% and -62.8%, respectively (p = 0.02 and 0.001, t test, n = 8 rats/group), whereas sham-operation eyes had no significant loss (mean difference between eyes = 1.7%, p = 0.74, t test). At eight days, inferior RGCs were unchanged from control, fellow eyes (mean interocular difference = -4.8%, p = 0.16, t test). Nine weeks after transection, inferior RGC had 34.5% fewer RGCs than their fellow eyes, compared to 41.2% fewer RGCs in the superior zones of the injured eyes compared to fellow eyes. Detailed, serial section studies of the topography of RGC axons in the optic nerve showed an orderly arrangement of fibers that were segregated in relation to the position of their cell bodies in the retina. CONCLUSIONS: A model of partial optic nerve transection in rats showed rapid loss of directly injured RGCs in the superior retina and delayed, but significant secondary loss of RGCs in the inferior retina, whose axons were not severed. These findings confirm similar results in monkey eyes and provide a rodent model in which pharmacological interventions against secondary degeneration can be tested.

Dr. H. Levkovitch-Verbin, Department of Ophthalmology, Wilmer Institute, Johns Hopkins Hospital, Baltimore, MD, USA


Classification:

2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
3.1 Microscopy (Part of: 3 Laboratory methods)
5 Experimental glaucoma; animal models



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