Abstract
Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma.
Highlights
Glaucoma is a progressive, neurodegenerative disease of the optic nerve, which is characterized by retinal ganglion cell (RGC) apoptosis [1,2,3,4,5,6]
From the initial animal and human studies that we have presented, considerable evidence shows that annexin A5 can successfully be used to visualize annexin-positive retinal cells using the Detection of Apoptosing Retinal Cells (DARC) technique
RGC apoptosis has been identified in the experimental models of disease and in patients clinically suffering from progressing glaucoma
Summary
Neurodegenerative disease of the optic nerve, which is characterized by retinal ganglion cell (RGC) apoptosis [1,2,3,4,5,6]. Intraocular pressure has been suggested to cause damage to axons within the lamina, interrupting axonal transportation, which is known to occur early in experimental glaucoma and has been found in post-mortem specimens [21,22] Another theory involves excitotoxicity, which implicates excess glutamate activity (the main excitatory neurotransmitter in the central nervous system) in the triggering of apoptosis [23,24]. SAP is carried out on each eye separately, which involves presenting targets to the patient, who presses a button in response to its appearance at certain locations This is mapped out for assessment by the clinician and for automated progression analysis [31,32]. Optimal glaucoma management involves early and accurate diagnosis [37] This enables IOP-lowering treatment to be targeted to the patients with progressive disease. The Detection of Apoptosing Retinal Cells (DARC) project has proposed an objective, pressure-independent method for detecting rates of glaucomatous degeneration in real-time, using fluorescently-labelled annexin A5 to quantify apoptosing RGCs
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