Effect of glatiramer acetate on primary and secondary degeneration of retinal ganglion cells in the rat.
OBJECTIVE
After crush injury to the optic nerve, elevated intraocular pressure, and glutamate toxicity, the immune modulator glatiramer acetate (GA, Cop-1; Copaxone; Teva Pharmaceutical Industries, Pitach Tikva, Israel) has been shown to reduce the delayed cell death of retinal ganglion cells (RGCs). This study was undertaken to confirm the protective effect of GA on secondary degeneration of RGCs in the rat, by using a spatial, rather than temporal, model.


METHODS
A total of 131 Wistar rats divided into 10 groups underwent bilateral stereotactic injection of fluorescent tracer (Fluorogold; Fluorochrome, Denver, CO) into the superior colliculus to label RGCs. They received a concurrent subcutaneously injection of (1) GA mixed with complete Freund's adjuvant (CFA), (2) CFA alone, or (3) saline. One week later, the superior one third of the left optic nerve was transected in animals in the six partial transection groups. Optic nerves in four additional groups underwent full transection. Rats were killed and retinas harvested from both eyes 1 or 4 weeks after partial transection and 1 or 2 weeks after full transection. RGC densities were calculated from retinal wholemounts, and differences between right (control) and left (transected) eyes were compared across treatment groups.


RESULTS
Among the partial transection groups, differences in the mean percentage of RGC loss in the inferior retinas were not significant at 1 or 4 weeks (ANOVA; P = 0.20, P = 0.12, respectively). After full transection, there was significantly more RGC loss in the GA group than in the CFA group when comparing whole retinas at 1 week, but not at 2 weeks (two-tailed t-test; P = 0.04, P = 0.36, respectively).


CONCLUSIONS
There is no evidence that GA has a neuroprotective effect after optic nerve transection, either for primarily injured or secondarily involved RGC.
Blair
Michael
M
Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 600 N Wolfe St, Baltimore, MD 21287, USA.
Pease
Mary Ellen
ME
Hammond
John
J
Valenta
Danielle
D
Kielczewski
Jennifer
J
Levkovitch-Verbin
Hana
H
Quigley
Harry
H
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D019771:Axotomy; D002452:Cell Count; D016923:Cell Death; D005456:Fluorescent Dyes; D000068717:Glatiramer Acetate; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009900:Optic Nerve / Q000502:physiology / Q000601:surgery; D010455:Peptides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D000276:Adjuvants, Immunologic; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D010455:Peptides; D013266:Stilbamidines; D000068717:Glatiramer Acetate