Real-Time Imaging of Retinal Ganglion Cell Apoptosis

Abstract

Monitoring real-time apoptosis in-vivo is an unmet need of neurodegeneration science, both in clinical and research settings. For patients, earlier diagnosis before the onset of symptoms provides a window of time in which to instigate treatment. For researchers, being able to objectively monitor the rates of underlying degenerative processes at a cellular level provides a biomarker with which to test novel therapeutics. The DARC (Detection of Apoptosing Retinal Cells) project has developed a minimally invasive method using fluorescent annexin A5 to detect rates of apoptosis in retinal ganglion cells, the key pathological process in glaucoma. Numerous animal studies have used DARC to show efficacy of novel, pressure-independent treatment strategies in models of glaucoma and other conditions where retinal apoptosis is reported, including Alzheimer’s disease. This may forge exciting new links in the clinical science of treating both cognitive and visual decline. Human trials are now underway, successfully demonstrating the safety and efficacy of the technique to differentiate patients with progressive neurodegeneration from healthy individuals. We review the current perspectives on retinal ganglion cell apoptosis, the way in which this can be imaged, and the exciting advantages that these future methods hold in store.

Keywords: annexin; apoptosis; glaucoma; imaging; neurodegeneration; retinal ganglion cell.

Figure 1

DARC imaging highlighting apoptosing retinal ganglion cells (a) using intravitreal ANX776 in a rat model of glaucoma following episcleral vein injections of hypertonic saline; (b) using intravenous ANX776 in a human glaucoma patient shown to have progressive disease.

Figure 2

Potential RGC-neuroprotective agents and their targeted pathogenic processes, some of which have been studied with DARC imaging. (ROS: Reactive Oxygen Species).

Figure 3

Lifespan-adjusted projection of DARC counts extrapolated from a rodent model of glaucoma, and superimposed onto a human disease course over 30 years. This demonstrates potential for diagnosis of early disease using DARC.