The overall aim of this project is to establish a new method for obtaining repeatable quantitative measurements of retinal ganglion cell projections to the mouse brain in vivo. This will allow direct longitudinal assessment of optic nerve axon projections to the brain in mouse models of ocular disease characterized by gradual optic nerve degeneration.
Aim 1. To correlate the distribution and signal strength of an orthograde axonal tracer recognizable in MRI images with the number of axons present in the optic nerve. Using normal mice and mice that previously received graded optic nerve crush, these studies will correlate the strength of the MRI signal and the amount of tracer injected into the eye with the number of optic nerve axons as determined by electron microscopy.
Aim 2. To define the limitations of making multiple injections of the MRI tracer over time in order to obtain longitudinal assessments of optic nerve axon projections. These studies will evaluate the limits of experimental parameters within which one to four reproducible repeated optic nerve projection measurements can be made without inducing retinal or optic nerve damage. Experiments will be conducted in normal mice and mice that previously received graded optic nerve crush. They will include assessments of neuronal survival, neuronal morphology, and gliosis in the retina and in retinorecipient nuclei of the brain.
Aim 3. To assess the validity of the optimized parameters for the evaluation of optic nerve axon loss in a transgenic spontaneous mouse model of open angle glaucoma. These studies will correlate the distribution and signal strength of an orthograde axonal tracer recognizable in MRI images with the ? distribution and strength of a standard histological orthograde axonal tracer and the number of axons ? present in the optic nerve. ? ?
| Leung, Christopher Kai-shun; Lindsey, James D; Crowston, Jonathan G et al. (2008) Longitudinal profile of retinal ganglion cell damage after optic nerve crush with blue-light confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 49:4898-902 |
| Leung, Christopher K S; Lindsey, James D; Crowston, Jonathan G et al. (2008) In vivo imaging of murine retinal ganglion cells. J Neurosci Methods 168:475-8 |
| Liu, Quan; Ju, Won-Kyu; Crowston, Jonathan G et al. (2007) Oxidative stress is an early event in hydrostatic pressure induced retinal ganglion cell damage. Invest Ophthalmol Vis Sci 48:4580-9 |
