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Journal Club October – Developing a Glucosepane Breaker

On Wednesday, October 28th at 1:00 PM EDT, Dr. Oliver Medvedik returns with the Journal Club live on our Facebook page; the topic this month is glucosepane breakers and a recent paper that takes a step forwards in making them a reality. The new research takes us a step close to finding ways to remove the advanced glycation end-product known as glucosepane, a likely reason why our arteries stiffen as we age.

Although there is ample evidence that the advanced glycation end-product (AGE) glucosepane contributes to age-related morbidities and diabetic complications, the impact of glucosepane modifications on proteins has not been extensively explored due to the lack of sufficient analytical tools. Here, we report the development of the first polyclonal anti-glucosepane antibodies using a synthetic immunogen that contains the core bicyclic ring structure of glucosepane. We investigate the recognition properties of these antibodies through ELISAs involving an array of synthetic AGE derivatives and determine them to be both high-affinity and selective in binding glucosepane. We then employ these antibodies to image glucosepane in aging mouse retinae via immunohistochemistry. Our studies demonstrate for the first time accumulation of glucosepane within the retinal pigment epithelium, Bruch’s membrane, and choroid: all regions of the eye impacted by age-related macular degeneration. Co-localization studies further suggest that glucosepane colocalizes with lipofuscin, which has previously been associated with lysosomal dysfunction and has been implicated in the development of age-related macular degeneration, among other diseases. We believe that the anti-glucosepane antibodies described in this study will prove highly useful for examining the role of glycation in human health and disease.

Literature

Streeter, M. D., Rowan, S., Ray, J., McDonald, D. M., Volkin, J., Clark, J., … & Spiegel, D. A. (2020). Generation and Characterization of Anti-Glucosepane Antibodies Enabling Direct Detection of Glucosepane in Retinal Tissue. ACS Chemical Biology.

 

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