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.
Highlights
Background to GlaucomaGlaucoma is a progressive, sight-threatening neurodegenerative optic neuropathy thought to be predominantly characterized by apoptosis of retinal ganglion cells (RGCs) [1,2]
Sight-threatening neurodegenerative optic neuropathy thought to be predominantly characterized by apoptosis of retinal ganglion cells (RGCs) [1,2]
These specialized sensory neurons relay information to interneurons such as horizontal, bipolar and amacrine cells for further processing, the cell bodies of which constitute the inner nuclear layer [9]. These in turn relay processed visual information to the retinal ganglion cells, whose axons form the retinal nerve fiber layer, conveying signals to the brain via the optic nerve. These nerve fibers exit the globe via the lamina cribrosa, a mesh-like collagen structure that represents the weakest point of the sclera, where optic nerve fibers are purported to undergo mechanical stress; one of the several proposed triggers of retinal ganglion cell apoptosis [5]
Summary
Sight-threatening neurodegenerative optic neuropathy thought to be predominantly characterized by apoptosis of retinal ganglion cells (RGCs) [1,2]. It is classically associated with loss of retinal nerve fiber layer and optic disc ‘cupping’, leading to characteristic mid-peripheral arcuate visual field defects [3]. Estimates suggest worldwide sufferers could total 111.8 million by the year 2040, demonstrating the necessity for more sophisticated ways to image this condition, especially at a cellular level This is required in order to earlier identify those in need of treatment, and minimize visual loss. 4.4% still progressed to glaucomatous damage and vision loss [6], emphasizing the importance of understanding the contributing pressure-independent mechanisms and how to target them with treatment [7,8]
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