Abstract
Purpose: :
To characterize the histological changes that occurs following induction of ischemic or mechanical optic nerve injury in transgenic mice.
Methods: :
Anterior ischemic optic neuropathy (AION) or crush injury was induced in the right eye of transgenic mice labeled for Thy1-CFP or CNPase-GFP, respectively. The left eye served as a control. The eyes were enucleated in a temporal manner, and the brain with the optic nerves was completely dissected. Cryopreserved sections of both optic nerves were stained for evaluation of apoptosis and analyzed for axonal and cell loss under fluorescence microscopy. Flat-mounted retinas of the retinal-ganglion-cell-labeled Thy1-CFP mice were also analyzed for retinal ganglion cell loss.
Results: :
Following the induction of optic nerve damage, axonal loss was detected in the Thy1-CFP-labeled mice and demyelination was detected in the CNPase-GFP mice, at the same time points. The damage proceeded retrogradely and, in the crush-injury group, crossed the chiasm within 4 days. At two weeks after induction of damage, 70% retinal ganglion cell loss was noted in the crush-injury group compared to 30% loss in the rAION group. Maximal apoptosis of the optic nerve cells was detected on day 3.
Conclusions: :
Axonal injury and demyelinization along the optic nerves occurs simultaneously after ischemic and mechanical injury in different types of transgenic labeled mouse models. The degree of retinal ganglion cell loss indicates the severity of the injury. Transgenic mice offer a promising means to explore the progressive damage following optic nerve injury. Fluorescence labeling enables better understanding of the pathophysiology of this process and may help clinicians develop potent neuroprotective agents.
Keywords: optic nerve • neuro-ophthalmology: optic nerve • transgenics/knock-outs