Tracking retinal microgliosis in models of retinal ganglion cell damage

Abstract

Purpose. To investigate the longitudinal profiles of microgliosis after optic nerve injury induced by optic nerve crush and acute elevation of intraocular pressure (IOP). Methods. A confocal scanning laser ophthalmoscope was used to image the retinal microglia of the CX3CR1GFP/+ transgenic mice in vivo at baseline, 3 days and then weekly for 4 weeks after optic nerve crush (n = 3), and after elevating the IOP to 110 mm Hg for 30 (n = 3) or 60 (n = 3) minutes. Results. After optic nerve crush, the density of microglia increased by 2.43 ± 0.19-fold at week 1 and then gradually declined with 2.04 ± 0.24-, 1.69 ± 0.25-, and 1.29 ± 0.11-fold increases at week 2, 3, and 4, respectively. Microgliosis followed a similar pattern after acute IOP elevation and the increase in microglia was associated with the duration of IOP elevation. There were 1.35 ± 0.17- and 2.03 ± 0.08-fold increases in microglia at week 1, and 1.15 ± 0.11- and 1.11 ± 0.10-fold increases at week 4, after 30 and 60 minutes of acute IOP elevation, respectively. The morphology of microglia changed from ramified to ameboid form in 1 week, and then returned to ramified form in the subsequent weeks. There was a significant negative association between the number of surviving retinal ganglion cells (RGCs) and the extent of microgliosis during the follow-up period (R2 = 0.72, P = 0.004). Conclusions. Longitudinal in vivo imaging of the retinal microglia can provide an effective approach to study microgliosis and its association with RGC degeneration. Copyright 2012 The Association for Research in Vision and Ophthalmology, Inc.