Purchase this article with an account.
Qiuhong Li, Amrisha Verma, Ping Zhu, Pollob Shil, Neha Kohli, Donevan Westerveld, Henry Daniell; Oral delivery of bioencapsulated myelin basic protein ameliorate amyloid burden and RGC loss in transgenic mouse model of Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5963. doi: https://doi.org/.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Increased deposition of amyloid beta 42 (Aβ42) is associated with RGC apoptosis and retinal structural and functional impairments. Myelin basic protein (MBP), a major structural protein of CNS, also possesses intrinsic protease activity capable of degrading Aβ amyloid, binds Aβ amyloid and inhibit Aβ fibril formation. We aimed to investigate the protective effect of oral delivery of bioencapsulated MBP fused with the transmucosal carrier cholera toxin B subunit (CTB) in triple transgenic (3xTg) mouse model for Alzheimer's disease (AD).
CTB-MBP fusion protein was expressed in chloroplasts of tobacco. CTB-GFP expressed from chloroplasts of tobacco was also used as control. The 3xTg AD mice (12-14 months old) were fed with CTB-MBP bioencapsulated in plant cells for 3 months. Aβ42 aggregates were evaluated by ELISA and western blotting of fractionated brain and retinal proteins, as well as immunofluorescence of frozen sections using antibodies specific to Aβ42. Retinal morphology, apoptosis and RGC density were evaluated from fixed sections.
Orally delivered CTB- GFP bioencapsulated in plant cells was detected in brains and retinae of healthy mice. Brain Aβ levels were reduced in 3xTgAD mice fed with bioencapsulated CTB-MBP, especially the Aβ-42 insoluble fraction. The amyloid plaque intensity was reduced in a concentration dependent manner by CTB-MBP incubation with human AD and 3xTgAD mice brain sections. CTB-MBP oral delivery reduced Aβ-42 accumulation in retinae and prevented loss of retinal ganglion cells. Lyophilization of leaves increased CTB-MBP concentration by 17-fold and facilitated long term storage at room temperature in capsules.
Orally delivered CTB-MBP was able to reduce Aβ42 aggregates in the brain and retina and prevent RGC loss in the aged 3xTg AD mouse. Bioencapsulation protected fusion protein from acids and enzymes in the digestive system and CTB fusion facilitated uptake by target cells including brain and retina, thus this technology provides a novel, more efficient, environmentally friendly and cost-effective delivery of therapeutic proteins free of human or animal pathogens to treat neurodegenerative diseases.
This PDF is available to Subscribers Only