Differential effects of microglia/macrophages in the prevention of retinal ganglion cell loss in rats with laser-induced chronic ocular hypertension

Abstract

Although it is known that microglia/macrophages produce neuroprotective effects in acute injury, whether they do the same in chronic neurodegeneration such as glaucoma is largely unknown. Cataractogenic lens injury has been demonstrated in an optic nerve crush model to prevent retinal ganglion cell (RGC) loss probably mediated by microglia/macrophages. Using a laser-induced chronic ocular hypertension (COH) model, we systematically studied the influences of microglia/macrophages in RGC loss. Similar to optic nerve crush injury, cataractogenic lens injury provided neuroprotective effects on RGCs, probably mediated by the mild activation of microglia/macrophages. While a small number of microglia did not produce significant influence, injection of large number of microglial cells into the vitreous significantly increased RGC loss. Appropriate quantity (104 microglial cells per intraocular injection) markedly reduced RGC loss in the COH model. Monocyte chemoattractant protein 1 (MCP1) at low concentration (10ng and 100ng) provided significant neuroprotective effect on RGCs, which may attribute to the chemoattractive property on monocytes/macrophages to the retina. Potent stimulation of microglia/macrophages by lipopolysaccharide (LPS) increased the death of RGCs in the COH model. These results advance our understanding of the roles of microglia/macrophages in chronic neurodegeneration. Our results may pave a new road for therapeutic strategy in chronic neurological disorder like glaucoma. Supported by The study is fully supported by The Glaucoma Foundation, USA, to R.C.C. Chang