Tracking Dendritic Shrinkage of Retinal Ganglion Cells after Acute Elevation of Intraocular Pressure

Abstract

To investigate dendritic changes of retinal ganglion cells (RGCs) and the rate of dendritic shrinkage after retinal ischemia induced by acute elevation of intraocular pressure (IOP). After elevating the IOP to 110 mm Hg for 30, 60, 90, and 120 minutes, a confocal scanning laser ophthalmoscope (CSLO) was used to serially image the retinas of the Thy-1 YFP transgenic mice in vivo for 1 to 3 months. Dendritic and axonal arborizations of 52 RGCs were visualized and followed longitudinally. Dendritic field, dendritic branching complexity (modified Sholl analysis), axonal diameter, and cell body area were measured. A total of 426 longitudinal measurements of dendritic field and dendritic complexity were analyzed for estimation of rate of change with linear mixed modeling. There were no morphologic changes of RGCs after 30 (n = 12) or 60 (n = 12) minutes of ischemia. After 90 minutes of ischemia (n = 19), 78.9% of RGCs showed progressive loss of dendrites, axon, and cell body, 5.3% had only mild reduction of branching complexity and shrinkage of dendritic field whereas 15.8% showed no morphologic changes. All RGCs lost dendritic and axonal arborizations after 120 minutes of ischemia (n = 9). The rates of reduction of dendritic field were 11.7% per day (95% confidence interval, 5.0%-18.4% per day) after 90 minutes, and 15.1% per day (10.3%-19.9% per day) after 120 minutes of ischemia. RGCs demonstrated dendritic shrinkage after 90 to 120 minutes, but not after 30 to 60 minutes of ischemia. In vivo imaging of dendritic changes could provide a sensitive approach to measure the rate of dendritic shrinkage after acute IOP elevation.