Tracking Retinal Microglia Activation in Optic Nerve Injury

Abstract

 

Purpose:

 

To investigate the longitudinal profiles of microglia activation after optic nerve injury induced by optic nerve crush and acute elevation of intraocular pressures (IOP).

 

Methods:

 

A confocal scanning laser ophthalmoscope was used to image the retinas of the CX3CR1^GFP/+ transgenic mice in vivo at baseline and then weekly for 4 weeks after optic nerve crush and after elevating the intraocular pressure to 110 mmHg for 30, 60, 90 and 120 minutes. The number of microglia was counted at the same retinal locations longitudinally.

 

Results:

 

After optic nerve crush, the density of microglia increased by 2.4+/-0.3 fold at week 1 and then gradually declined with 2.0+/-0.2, 1.6+/-0.4 and 1.4+/-0.1 fold increase at week 2, 3 and 4, respectively. Microglia proliferation followed a similar pattern after acute IOP elevation and the increase in microglia was proportional to the duration of IOP elevation. The morphology of the 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 correlation between the number of surviving retinal ganglion cells (RGCs) and the total number of activated microglia in the follow-up period (Spearman's correlation coefficient=-0.712).

 

Conclusions:

 

The microglia activated in a week and then returned to near the baseline level in 4 weeks following optic nerve injury. Microglia activation was associated with RGC degeneration.  

 

Keywords: retinal glia • retina: proximal (bipolar, amacrine, and ganglion cells) • imaging/image analysis: non-clinical