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NA 3 glycan: a potential therapy for retinal pigment epithelial deficiency
Author(s) -
Chintalapudi Sumana R.,
Wang XiangDi,
Wang XiaoFei,
Shi Yunfeng,
Kocak Mehmet,
Palamoor Mallika,
Davis Raven N.,
Hollingsworth T. J.,
Jablonski Monica M.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15006
Subject(s) - glycan , pigment , retinal , retinal pigment epithelium , chemistry , microbiology and biotechnology , biology , biochemistry , glycoprotein , organic chemistry
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 ( NA 3)—in two distinct preclinical models of atrophic AMD . In RPE ‐deprived Xenopus laevis tadpole eyes, NA 3 supported normal retinal ultrastructure. In RCS rats, NA 3 supported fully functioning visual integrity. Furthermore, structural analyses revealed that NA 3 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— NA 3—in two unique preclinical models with RPE insufficiency. These data suggest that NA 3 glycan therapy may provide a new therapeutic avenue in the prevention and/or treatment of retinal diseases such as atrophic AMD .