NA3 glycan: a potential therapy for retinal pigment epithelial deficiency.
Sumana R ChintalapudiXiangDi WangXiaoFei WangYunfeng ShiMehmet KocakMallika PalamoorRaven N DavisT J HollingsworthMonica M JablonskiPublished in: The FEBS journal (2019)
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.
Keyphrases
- age related macular degeneration
- small molecule
- optical coherence tomography
- drug administration
- cell surface
- cell therapy
- single molecule
- mesenchymal stem cells
- cell proliferation
- blood brain barrier
- cell death
- cell cycle arrest
- bone marrow
- stem cells
- deep learning
- replacement therapy
- protein protein
- big data
- subarachnoid hemorrhage
- combination therapy
- endoplasmic reticulum stress