# Fructosyl Amino Oxidase as a Therapeutic Enzyme in Age-Related Macular Degeneration

## TL;DR

Fructosyl amino oxidase (FAOD) may help treat age-related macular degeneration by breaking down harmful AGEs in the retina.

## Contribution

FAOD is shown to reduce AGE accumulation in retinal tissue, offering a novel therapeutic approach for AMD.

## Key findings

- FAOD treatment reduced AGE autofluorescence in porcine retinas (p = 0.001).
- FAOD significantly decreased drusen surface area in AMD-affected human retinas to 45 ± 21%.
- FAOD breaks down multiple AGEs, including fructosyllysine and imidazolone, more broadly than FN3K.

## Abstract

Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence (p = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch’s membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.