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Sau-Wai Yu, W.K. Wong, A.W.S. Cheung, E.Y.P. Cho; Suramin Is a Potent Stimulator Of Retinal Ganglion Cell Regeneration After Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):334.
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Suramin, an anti-parasitic drug and a non-specific P2 purinergic receptor antagonist, has been reported to have neuroprotective properties. However, whether suramin promotes regeneration of the central nervous system is not known. To address this, the influence of suramin on the survival and regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) injury was studied.
The ON of adult hamster was transected and suramin or its vehicle (saline) was injected intravitreally. At 1 week post-ON cut, RGC survival was quantified by βIII-tubulin immunostaining, and surviving RGCs that expressed the growth-associated protein GAP-43, a marker that correlates with regenerative propensity, were counted. Peripheral nerve (PN) grafting to the cut ON was used to assess whether suramin could potentiate the regeneration of RGC axons into the graft. Intravitreal injection of ciliary neurotrophic factor (CNTF, a potent growth factor for RGC regeneration), PPADS (non-specific P2 antagonist), or suramin analogues (with greater specificity towards selective P2 subtypes), were performed to compare with suramin.
Both Suramin and CNTF promoted moderate RGC survival (Fig.1A). Suramin, however, has a dramatic effect on RGC regeneration. The number of GAP-43 and regenerating RGCs were 400% and 800%, respectively, that of the control after suramin treatment (Figs.1B-C; 2). Suramin also stimulated more GAP-43 expression (150%) and RGC axonal regeneration into the PN (155%) compared to CNTF (Figs.1B-C; 2). In contrast, PPADS did not enhance GAP-43 expression and axonal regeneration of RGCs above that of control (Fig.3B-C), suggesting that suramin promoted regeneration independent of P2 antagonisation. This was also reflected in studies with suramin analogues in which no clear-cut pattern was seen (Fig.3): NF157 and NF279 promoted GAP-43 expression and regeneration similar to suramin, while NF023 and NF110 resembled the control.
Suramin promotes RGC axonal regeneration better than CNTF. The mechanism involved may be distinct from P2 blockade.
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