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Pollob Kumar Shil, Kwangchul Kwon, Ping Zhu, Amrisha Verma, Vinayak Shenoy, Mohan Raizada, Henry Daniell, Qiuhong Li; Oral Delivery of ACE2 or Ang-(1-7) Bioencapsulated in Plant Cells Protect against Experimental Uveitis and Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5999.
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The vasoprotective axis of the renin-angiotensin system (RAS) involving ACE2/Ang-(1-7)/Mas counteract the conventional proliferative, fibrotic, proinflammatory and hypertrophic effects of vasodeleterious axis of RAS consisting of ACE/AngII/AT1R. In this study, we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS, ACE2/Ang-(1-7), by receptor mediated oral delivery of bioencapsulated in plant cells would confer protection against endotoxin induced uveitis (EIU) and experimental autoimmune uveoretinitis (EAU).
Genes expressing ACE2 and Ang-(1-7), fused with cholera toxin subunit B (CTB) were cloned in a chloroplast transformation vector, pLD. The expression was evaluated by western blotting and activity assays. The effects of orally delivered CTB-ACE2/Ang-(1-7) on EIU and EAU models in C57B6/J and B10.RIII mice respectively were examined.
Increased levels of ACE2 and Ang-(1-7) were observed in circulation and retina after oral administration of CTB-ACE2/Ang-(1-7) leaf materials. Oral feeding of mice with bioencapsulated ACE2 or Ang-(1-7) significantly reduced LPS induced infiltration of inflammatory cells and expression of inflammatory cytokines in the eye; also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in EAU eyes.
These results demonstrate that enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells provide an innovative, more efficient and cost-effective therapeutic strategy for ocular inflammation such as uveitis and autoimmune uveoretinitis.
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