Detection of early glial responses in the retina,optic nerve and optic chiasm in acute ocular hypertension rat model / 中华实验眼科杂志

ABSTRACT

Background Glial cells perform specialized function in many aspects of the development,homeostasis,and function of neurons.Retinal ganglion cells (RGCs)and glia interactions are critically important in glaucomatous neurodegeneration.However,the precise mechanisms of glial activation and ganglion cells damage are still remained unclear. Objective This study was to assess the early responses of glial cells in the retina,optic nerve and optic chiasm in rat models of acute high intraocular pressure (IOP),and to examine the expression of nestin,a neuronal progenitor marker,in the reactive glias. Methods Acute high IOP of 110 mmHg was induced in the right eyes of 6 clean adult female Wistar rats by infusing normal saline solution into the anterior chamber for 60 minutes.Three normal matched Wistar rats were used as controls.The rats were sacrificed by overanaesthesia and sections of retina,optic nerve and optic chiasm were collected on 3 days and 7 days after the injection.Rat retina was examined by Nissl staining to illustrate the gross structure changes.Loss of axons of RGCs in the optic nerve was assessed by immunostaining of β Ⅲ-tubulin.Double labeling of glia] fibrillary acidic protein (GFAP) and nestin was performed in sections of retina,optic nerve and optic chiasm to evaluate the glial responses.The use of the animals complied with Statement of Animal Ethic Committee of Peking University Third Hospital. Results In control rats,GFAP-positive glial cells were observed in the retina,optic nerve and optic chiasm,where only weak positive response for nestin was noticed.Three days after acute IOP elevation,thickness of inner plexus form layer was significantlydecreased in comparison with the control rats.A loss of 46％ RGCs was found in the rats with ocular hypertension.Obvious increase of GFAP expression was displayed in the retina,and processes of GFAP-positive glia cells extended into outer retina accompanied with significant up regulation of nestin.Axons in the optic nerve demonstrated a tendency of degeneration.Nestin expression increased significantly in the GFAP-positive glias in the optic nerve.Cross-sectional area of optic chiasm corresponding to the injured retina decreased relative to its countcrpart.Astrocyte like GFAP and nestin-colabeled glials were observed in this part of optic chiasm.The pathological changes of the retina,optic nerve and optic chiasm in hypertensive eyes aggravated on 7 days. Conclusions Acute ocular hypertension induce early onset of RGCs loss and axon degeneration.Neuronal injury is accompanied with glial reaction.Reactive glial cells express neuronal progenitor markers.The structural changes of the optic nerve and optic chiasm occur simultaneously with the high IOP.