National Eye Institute Study Revisits Role of Annexin-V Biomarker in Retinal Cell Degeneration

Recent findings from a National Eye Institute-led study shed new light on annexin-V, a widely used biomarker to track apoptosis and retinal cell death in eye disease. The study group identified that annexin-V also binds to immune cells, suggesting it may a have a role as a marker for ocular inflammation. These results were published online in the International Journal of Biological Sciences.

“Now we discovered that annexin-V also binds to immune cells, which complicates our interpretation of findings when using this biomarker,” Kiyoharu Miyagishima, PhD, study co-first author and staff scientist in the NEI Retinal Neurophysiology Section, said in a recent press release. 

Traditionally, annexin-V is used as a marker for apoptosis (programmed cell death) in retinal ganglion cells because it can be fluorescently labeled. These cells connect the retina to the brain to process light and images; loss of these cells in pathology such as glaucoma is what leads to ultimate blindness. Over the past two decades, annexin-V has become a critical component of an imaging technique called DARC (detection of apoptosing retinal cells) that is used in basic research and clinical investigations. 

However, there remain a few uncertainties with the mechanism of action of annexin-V, which is what prompted the NEI group to revisit these studies. Unexpectedly, they found that in addition to apoptotic retinal ganglion cells, annexin-V also binds to immune cells and to a subset of microglial cells in the retina. Microglial cells are the earliest to respond to damages or changes in the cellular environment, suggesting annexin-V may have a role in detecting early inflammation. 

“These findings challenge the interpretation of DARC imaging counts of fluorescing annexin-V, and the role annexin-V should play in the diagnosis of retinal diseases,” the authors wrote in their paper.

At the same time, these findings may represent new opportunities to advance our understanding of retinal immune cells and their roles in therapeutics. While further study is needed, the authors suggest annexin-V has the potential to monitor microglial activation and neuroinflammation in neurodegenerative diseases like age-related macular degeneration or retinitis pigmentosa.