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Abstract #27999 Published in IGR 13-1
Similarities and differences between primary and secondary degeneration of the optic nerve and the effect of minocycline
Levkovitch-Verbin H; Spierer O; Vander S; Dardik RGraefe's Archive for Clinical and Experimental Ophthalmology 2011; 1-9
Purpose: To investigate the mechanism of secondary degeneration of the optic nerve, and to evaluate the neuroprotective effect of minocycline in this process. Methods: A partial transection model that morphologically separates primary and secondary degeneration was applied unilaterally in 152 Wistar rat eyes. The involvement of pro-apoptotic, pro-survival and inflammatory pathways was analyzed by quantitative real-time PCR and immunohistochemistry at multiple time points. The neuroprotective effect of daily intraperitoneal injections of minocycline 22 mg/kg/day was evaluated at 7, 11 and 21 days post-injury. Retrograde labeling of retinal ganglion cells (RGCs) with fluorogold was via the superior colliculus, and surviving RGCs were counted using retinal whole mounts. Results: Both primary and secondary degeneration led to a significant up-regulation of the pro-apoptotic genes, GADD45(alpha), ei24 and CDK2, and the pro-survival gene, IAP-1. These processes differed, however, in their reaction to minocycline. Minocycline protected RGC death from secondary degeneration at 11 days (6 (plus or minus) 8% loss compared to 37 (plus or minus) 7% in the saline-treated group, n = 15, P = 0.012), and at 21 days (42 (plus or minus) 7% versus 64 (plus or minus) 7% respectively, n = 15, P = 0.06) after partial transection. In contrast, its effect on primary degeneration was not significant. Conclusions: While the genetic profile supported similarities between primary and secondary degeneration of the optic nerve, the specific effect of minocycline on secondary degeneration revealed a potential difference between the two. The mechanism underlying secondary degeneration, and its role in optic neuropathies such as glaucoma, awaits further studies
H. Levkovitch-Verbin. Sam Rothberg Ophthalmic Molecular Biology Laboratory, Goldschleger Eye Institute, Sheba Medical Cent, Tel-Aviv University, Tel-Aviv, 52621, Tel-Hashomer, Israel. halevko@hotmail.com
Classification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)