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Abstract:

Purpose: We investigated the involvement of matrix metalloproteinase-2 (MMP-2) in axonal regeneration of retinal ganglion cells (RGC) after optic nerve (ON) injury. Methods: MMP-2 deficient mice and their corresponding WT were subjected to an experimentally induced optic nerve crush (ONC) characterized by partial regeneration of RGC axons (RONC model) via intravitreal injection of Zymosan. RGC axonal regeneration was evaluated by anterograde labeling with CTB on ON cryosections at 14 and 42 dpi. RGC survival was determined by Brn3a IHC on whole mount retinas. Retinal and ON MMP-2 expression was evaluated at different time points after RONC. Leukocyte infiltration after RONC was determinated by IHC for CD45. Results: Axon outgrowth was significantly reduced near the crush site in MMP-2 deficient as compared to WT mice, both at 14 and 42 dpi. Also the number of regenerating axons was dramatically reduced at various distances from the crush site upon MMP-2 deficiency. No difference in the number of Brn3a+ surviving RGCs was observed between both genotypes at 14 dpi. Moreover MMP-2 expression was highly increased in the processes of Müller glia and in the ON at 7 and 14 dpi respectively. Strikingly MMP-2 was found to be expressed in CD-45(+) infiltrating cells in the vitreous after RONC. Conclusions: MMP-2 expressed by infiltrating cells could contribute to the induction of axonal regeneration in the RONC model. MMP-2 seems to play a beneficial role in RGC axonal regeneration after ONC without affecting RGC survival. Our data suggest a pleotropic role for MMP-2 in RGC regeneration.