In Sumana R. Chintalapudi, XiangDi Wang; XiaoFei Wang; Yunfeng Shi, Mehmet Kocak; Mallika Palamoor; Raven N. Davis; T.J. Hollingsworth; Monica M. Jablonski.
Atrophic age-related macular degeneration (AMD) is the most common type of AMD, yet there is no United States Food and Drug Administration (FDA)-approved therapy. This disease is characterized by retinal pigment epithelial (RPE) insufficiency, primarily in the macula, which affects the structure and physiology of photoreceptors and ultimately, visual function. In this study, we evaluated the protective effects of a naturally derived small molecule glycan therapeutic – asialo-, tri-antennary complex-type N-glycan (NA3) – in two distinct preclinical models of atrophic AMD. In RPE-deprived Xenopus laevis tadpole eyes, NA3 supported normal retinal ultrastructure. In RCS rats, NA3 supported fully functioning visual integrity.
Furthermore, structural analyses revealed that NA3 prevented photoreceptor outer segment degeneration, pyknosis of the outer nuclear layer, and reactive gliosis of Müller cells (MCs). It also promoted maturation of adherens junctions between MC and photoreceptors. Our results demonstrate the neuroprotective effects of a naturally derived small molecular glycan therapeutic-NA3-in two unique preclinical models with RPE insufficiency. These data suggest that NA3 glycan therapy may provide a new therapeutic avenue in the prevention and/or treatment of retinal diseases such as atrophic AMD.
Dr. Jablonski is an IRRF-supported scientist at the University of Tennessee – Memphis.
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