Pathological changes of retinal glial cells in a rat chronic ocular hypertension model

OBJECTIVE: To study the pathological changes of retinal glial cells and its effect on retinal ganglion cells (RGC) damage in a rat chronic ocular hypertension model. METHODS: Seventy-two of Sprague-Dawley (SD) rats with chronic elevated intraocular pressure (IOP) by ligating two superior or inferior episcleral veins were used in this study. Twelve normal rats served as control. The densities of glial cells were determined in flat mounted or transverse semithin sections of retinas, microglial cells were visualized by OX42 staining on whole-mounted retinas, and Muller cells were detected by expressing glial fibrillary acidic protein (GFAP) on frozen section or flat mounted retinas with confocal microscopy at 2 hours, 12 hours, 1 day, 1 week, 4 weeks, and 8 weeks after operation, respectively. RESULTS: Compared with control group, the densities of activated microglial cells were significantly (F = 196.56, P 0.05) at all time points. The activated microglial cells were appeared at 2 hour while the activated Miller cells and astrocytes presented at 12 hours after operation. The activated Muller cells and astrocytes reached a peak value at 4 weeks, and then decreased gradually. The activated astrocyte had morphological changes including disappeared star-structure of cell body, stiffness, and shortness of cell processes. CONCLUSIONS: The alteration of microglial cell densities appears to be the earliest pathological changes of retina in rat with chronic ocular hypertension. The activated astrocytes with morphological disorder may deteriorate the damage of RGC and result in a harmful microenvironment for axonal regeneration of RGC in glaucoma.