The potential of annexin-labelling for the diagnosis and follow-up of glaucoma

Abstract

Glaucoma is one of the leading causes of blindness in developed countries and is mainly attributable to the apoptosis of retinal ganglion cells (RGCs). Although several diagnostic tools have been developed to detect and monitor this disease, none has the requisite sensitivity to identify it at a preclinical stage or to perceive small changes in retinal health over short periods. Specifically, irreversible visual changes occur before neuronal damage is discovered. The most widely accepted in vitro assay for apoptotic cells involves the use of fluorescent annexin A5. The radiolabelling of this marker makes it possible to assess, in vivo and non-invasively, various diseases in which the apoptotic process is pivotal, such as myocardial infarction or tumour response to chemotherapy. Recently, a new technique has been developed to visualise directly individual RGCs undergoing apoptosis in the living eye. This DARC (detection of apoptosing retinal cells) technology uses fluorescently labelled annexin A5 to bind apoptosing retinal neurons and confocal scanning laser ophthalmoscopy to detect the marked dying cells. Based on experimental models, DARC has been suggested to offer a direct and quantitative assessment of the retinal condition of patients. A Phase I clinical trial in glaucoma patients is scheduled to start shortly. This technology has the potential to pre-empt the diagnosis of glaucoma prior to visual deterioration, to provide an accurate numeric evaluation highlighting even small retinal changes and to allow the rapid judgement of the efficacy of both current and new therapeutic strategies.

Severe, Early Axonal Degeneration Following Experimental Anterior Ischemic Optic Neuropathy

“…Annexin-V has previously been shown to label dying RGC cell bodies in many conditions, 6,25,30,[32][33][34][35][40][41][42] and our data demonstrated for the first time that annexin-V intensely labeled degenerating RGC axons after AION. Annexin-V staining was well visualized in vivo using cSLO and in vitro in retinal whole mount preparations 7 days after AION, and the staining pattern along degenerating axons was most prominent near the optic nerve head and occurred in a fragmented pattern, consistent with Wallerian-like degeneration.…”

“…[27][28][29] Annexin-V has been used to label dying RGCs in vitro 6 and in vivo 30,31 after optic nerve transection, 6 retinal laser photocoagulation, 32 NMDA-induced excitotoxicity, 33 experimental AION, 25 and experimental glaucoma. 34,35 However, annexin-V has had limited use in labeling degenerating axons in the peripheral and central nervous system. In this paper, we present our data on evidence of early axonal degeneration and annexin-V labeling of RGC axons following experimental AION.…”

MicroRNA target prediction in glaucoma

“…The hypothesis of neuroprotective therapies (Baltmr et al, 2010) along with development of early diagnosis methods for glaucoma is growing. In fact, Normando et al have developed an early noninvasive diagnostic method to detect in vivo apoptotic RGCs, this method was useful in several preclinical models of glaucoma, and a phase I clinical trial has been scheduled to start soon (Normando et al, 2013). The role of apoptosis in AMD is controversial.…”

Neuroprotection in glaucoma

“…The optical properties of retinal tissue and the potential of adaptive optics are further discussed in the article by Prasse et al (2013). Normando et al (2013) focus in their article on the potential of annexin-labeling for the diagnosis and follow-up of glaucoma. This method allows the visualization of those retinal ganglion cells that are in the process of apoptotic death.…”