Assessing retinal ganglion cell damage

Abstract

Retinal ganglion cell (RGC) loss is the hallmark of optic neuropathies, including glaucoma, where damage to RGC axons occurs at the level of the optic nerve head. In experimental glaucoma, damage is assessed at the axon level (in the retinal nerve fibre layer and optic nerve head) or at the soma level (in the retina). In clinical glaucoma where measurements are generally limited to non-invasive techniques, structural measurements of the retinal nerve fibre layer and optic nerve head, or functional measurements with perimetry provide surrogate estimates of RGC integrity. These surrogate measurements, while clinically useful, are several levels removed from estimating actual RGC loss. Advances in imaging, labelling techniques, and transgenic medicine are making enormous strides in experimental glaucoma, providing knowledge on the pathophysiology of glaucoma, its progression and testing new therapeutic avenues. Advances are also being made in functional imaging of RGCs. Future efforts will now be directed towards translating these advances to clinical care.

Figure 1

Example of a standard automated perimetry printout from the left eye of a patient with a superior arcuate scotoma due to open-angle glaucoma. Text bubbles describe the main parameters evaluated.

Figure 2

Example of an optical coherence tomography (OCT) printout evaluating retinal nerve fibre layer (RNFL) thickness and optic nerve head neuroretinal rim (NRR) width from the same eye shown in Figure 1. There is a significant reduction of RNFL thickness and NRR width in the inferior sectors. Text bubbles describe the main parameters evaluated.

Figure 3

In vivo fluorescence imaging of the retina in a transgenic mouse expressing cyan fluorescent protein (CFP) under the Thy-1 promoter. Images were acquired longitudinally beginning at baseline (BL) and then 3, 7, 10, 14, and 21 days after optic nerve transection. (From Chauhan et al).

Figure 4

In vivo fluorescence imaging of the retina in a transgenic mouse expressing yellow fluorescent protein (YFP) under the Thy-1 promoter. Images were acquired longitudinally, beginning at baseline (BL) and then 3, 5, 7, 14, and 28 days after optic nerve transection.

Figure 5

In vivo fluorescence images of GFP-labelled retinal neurons in mouse following intravitreal injection of an adeno-associated viral vector with a ubiquitous promoter (AAV2-CAG-GFP) at (a) 1 week post-injection and (b) 5 weeks post-injection.

Figure 6

In vivo fluorescence imaging of the retina a transgenic mouse expressing GCaMP under the Thy-1 promoter (a) with baseline fluorescence in darkened room and (b) during exposure to UV light stimulus. Arrows indicate cells with decreased intracellular calcium and circles indicate cells with increased intracellular calcium during UV light exposure.