Ophthalmology in China

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Macrophage activation promotes retinal ganglion cell survival and axon regeneration after optic nerve injury

CEN Ling-ping, LIANG Jia-jian, ZHANG Ming-zhi.   

  1. Joint Shantou International Eye Center, Shantou University and The Chinese University of Hong Kong, Shantou 515041, China
  • Received:2016-03-22 Online:2016-08-25 Published:2016-08-02
  • Contact: CEN Ling-ping, Email: cenlp@hotmail.com

Abstract: Objective To investigate the relationship between macrophage activation status and neural repair after optic nerve injury. Design Experimental study. Participants 23 Fischer rats. Methods Optic nerve (ON) of Fischer rat was transected and grafted with an autologous peripheral nerve(PN) and let to survive for three weeks. Zymosan (ZYM) and macrophage inhibitory factor (MIF) were injected intraocularly after PN-ON procedure to change the macrophage activation status. To retrograde label the regenerating retinal ganglion cells(RGCs), fluorogold(FG) was slowly injected into the distal end of the PN graft three days before the perfusion. The amount of survival and regenerating RGCs and macrophages on the flat mounted retinas were counted after the perfusion and immunofluorescence staining. The experiment was divided into normal saline control group, ZYM group, MIF group, ZYM+MIF group. Main Outcome Measures Number of macrophage, surviving RGCs and axon-regenerating RGCs. Results Number of macrophages, surviving RGC and axon regenerating RGC in the control group are 91±6.1/mm2, 185±9.0/mm2 and 35±2.9/mm2 respectively. Compared to the control group, ZYM group obviously increased the number of intraocular macrophages by nearly ten folds (883±93.9/mm2), along with enhanced RGC survival (299±13.1/mm2) and axon regeneration (99±13.5/mm2). MIF group itself did not change RGC survival and axon regeneration. When macrophages were activated, however, combine application of MIF can substantially decrease the promoting effects of macrophage on axon regeneration (67±2.2/mm2), though the number of macrophages was not decreased (828±72.9/mm2). Conclusion Macrophages activated by ZYM can promote RGC survival and axon regeneration. Inhibition of macrophage activation by MIF leads to obvious down-regulation of axon regeneration of ON injury. (Ophthalmol CHN, 2016, 25: 237-240)

Key words: retinal ganglion cell, macrophage, optic nerve injury, axon regeneration