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M. Watanabe; Nipradilol Promotes Survival and Axonal Regeneration of Axotomized Ganglion Cells in Cat Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5211.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Nipradilol is an NO-donor, blocker of alpha and beta adrenoreceptors, and used as an ocular hypotensive drug. It also protects cell death of retinal ganglion cells (RGCs) induced by transection of the optic nerve (ON) (Nakazawa et al., '02). I examined what types of cat RGCs are rescued by nipradilol injected into the eye, and whether nipradilol promotes axonal regeneration of cat RGCs. Methods: Cats were anesthetized with a mixture of 1% halothane, 0.5 L/min nitrous oxide, and 1 L/min oxygen. ON Transection: The left ON was totally cut 7 days after DiI suspension was injected into the LGN. Nipradilol solution, 10 exp (-7) or 10 exp (-8) mol/eye, was injected 15 - 30 min before the transection. Peripheral Nerve Transplantation: After the ON transection, a segment of the common peroneal nerve was sutured to the cut end. Number of Surviving RGCs: Ratios of total cell numbers in the ON-transected retina vs the intact retina were obtained as ratios of densities of DiI-labeled RGCs in the area centralis. Number of Regenerating RGCs: Numbers of regenerated RGCs were estimated with counting labeled cells in 0.23 mm2 area separated 1 mm each. Double labeling: RGCs extending axon to 10 mm (10R-RGC) or those to 20 mm (20R-RGC) were labeled with fluorescent dyes injected into the graft at 10 mm or 20 mm separately. Results: Survival Promotion: An injection of nipradilol, 10 exp (-7) or 10 exp (-8) mol, promoted surviving RGCs: 60% survival in injected retinas while 43% in control retinas on day 7, 41% in injected retinas while 16% in control retinas on day 14. Survival of the beta cells was enhanced both on day 7 and 14, and survival of the alpha cells and not alpha/beta cells was also enhanced on day 14. Promotion of Axonal Regeneration: An injection of nipradilol increased numbers of regenerated RGCs 4 and 6 weeks after the transplantation. Average numbers of 10R-RGCs in nipradilol injected retinas were 8,962 (N=2) at week 4, and 12,384 (N=3) at week 6, while those in no injected retinas were 2,138 (N=6) at week 4 and 3,678 at 6 week, respectively. The ratio of 20R-RGCs in 10R-RGCs represents proportion of RGCs with 20 mm-long regenerated axons in RGCs with 10 mm or longer regenerated axons. The average ratios of 20R-RGCs in 10R-RGCs in the injected retinas were 38% (4 week) and 83% (6 week), higher than in no injected (control) retinas, 17% (4 week) and 65% (6 week). It was estimated that the first regenerated axons of nipradilol-treated RGCs reached 20 mm at week 2.3 while at week 3.3 in control. Conclusions: Nipradilol promotes both survival and axonal regeneration of axotomized RGCs. It should be clarified whether NO or blocking the receptors promote axonal regeneration.
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