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Z. Li, Q. Cui, Y. Yin, L. I. Benowitz; Macrophages and Oncomodulin Mediate the Effects of Lens Injury in Stimulating Axon Regeneration Through a Peripheral Nerve Graft. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3229.
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The purpose of this study was to investigate whether the effects of lens injury in promoting axon regeneration through a PN graft are dependent upon macrophages and/or oncomodulin (OM).
The left ON was exposed and transected 1.5 mm behind the optic disk. A 1.5 cm piece of autologous peroneal nerve was dissected out from left leg and sutured onto the ON stump with 10/0 suture. Rats survived for 3 weeks after injury. To block macrophage recruitment in the eye, we injected clodronate liposomes intravenously at time points before and after lens injury. PBS liposomes served as controls. Clodonate liposomes cause apoptotic death of blood monocytes and tissue macrophages when phagocytosed in sufficient numbers. Animals received intraocular injections of peptide that blocks the action of oncomodulin when need. RGCs that successfully regenerated their axons were identified by retrograde labeling. FluoroGold (FG) was injected into the distal end of the grafts 3 days prior to sacrifice. After counting FG-labeled RGCs, the retinas were double-immunostained with TUJ1 antibody to β tubulin to identify viable RGCs and ED1 to label macrophages.
Lens injury induced a substantial increase of the RGCs survival and axon regeneration into PN graft, as well as an infiltration of macrophage in retina. A peptide derived from N-terminus of OM (P1) inhibited the beneficial effect of lens injury. A similar effect of P1 on RGCs was observed in vitro.
1. Lens injury promotes RGC survival and axonal regeneration into a PN graft. 2. Lens injury enhances macrophage invasions into the eye after optic nerve injury. 3. The lens injury-induced RGC axonal regeneration is achieved via macrophage recruitment in the eye. 4. OM is responsible for most of the effect of LI on axon regeneration.
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