Activation of microglia/macrophages determines the fate of retinal ganglion cell survival in rat chronic ocular hypertension model

摘要

Although it has been demonstrated that microglia/macrophagesproduce neuroprotective effects in acute injury, whetherthey do the same in chronic neurodegeneration such as glaucomais largely unknown. Using a laser-induced chronic ocular hypertension(COH) model, we systematically studied the influences ofmicroglia in RGC loss. Adult female SD rats were anesthetizedwith intra-peritoneal injection of a ketamine/xylazine mixture.Proparacaine hydrochloride was applied to the eyes as topical anesthetics.The limbal vein and the three radial episcleral aqueoushumor drainage veins of the right eye were photocoagulated twicewith a 7-day interval using an Argon laser. While a small numberof microglial cells (10 3 ) did not produce significant influence, injectionof large number of microglial cells (10 5 ) into the vitreoussignificantly increased RGC loss. Appropriate quantity (10 4 ) microglialcells per intraocular injection markedly reduced RGC lossin the COH model. Monocyte chemoattractant protein 1 at lowconcentration (10 and 100 ng), but not at high concentration (1,000ng), provided significant neuroprotective effect on RGCs, whichmay attribute to the chemoattractive property on microglia/macrophagesto the retina. Immunocytochemical staining on flatmounted retinas displayed high immunoreactivity for ionized calciumbinding adapter molecular 1 (Iba1), indicating high numberof microglia/macrophages. Potent stimulation of micro glia/macrophagesby lipopolysaccharide (LPS) significantly increased thedeath of RGCs in the COH model. Iba1-immunoreactive positivemicroglia/macrophages in the LPS group were activated with enlargedcell body and thickened short process. These results advanceour understanding of the roles of microglia in chronic neurodegeneration.Our results can demonstrate that microglia/macrophagescan be either protective or harmful depending on thestimulation in chronic neurological disorder like glaucoma. Acknowledgement: The study is supported by The AmericanHealth Assistant Foundation to R.C.C. Chang and K.-F. So.