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Hyperactivity of the renin-angiotensin system (RAS) resulting in elevated Angiotensin II (Ang II) contributes to all stages of inflammatory responses including ocular inflammation. The discovery of angiotensin-converting enzyme 2 (ACE2) has established a protective axis of RAS involving ACE2/Ang-(1–7)/Mas that counteracts the proinflammatory and hypertrophic effects of the deleterious ACE/AngII/AT1R axis. Here we investigated the hypothesis that enhancing the systemic and local activity of the protective axis of the RAS by oral delivery of ACE2 and Ang-(1–7) bioencapsulated in plant cells would confer protection against ocular inflammation. Both ACE2 and Ang-(1–7), fused with the non-toxic cholera toxin subunit B (CTB) were expressed in plant chloroplasts. Increased levels of ACE2 and Ang-(1–7) were observed in circulation and retina after oral administration of CTB-ACE2 and Ang-(1–7) expressing plant cells. Oral feeding of mice with bioencapsulated ACE2/Ang-(1–7) significantly reduced endotoxin-induced uveitis (EIU) in mice. Treatment with bioencapsulated ACE2/Ang-(1–7) also dramatically decreased cellular infiltration, retinal vasculitis, damage and folding in experimental autoimmune uveoretinitis (EAU). Thus, enhancing the protective axis of RAS by oral delivery of ACE2/Ang-(1–7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for ocular inflammatory diseases.
© <2014>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Shil, P. K., Kwon, K., Zhu, P., Verma, A., Daniell, H., & Li, Q. (2014). Oral Delivery of ACE2/Ang-(1–7) Bioencapsulated in Plant Cells Protects Against Experimental Uveitis and Autoimmune Uveoretinitis. Molecular Therapy, 22 (12), 2069-2082. http://dx.doi.org/10.1038/mt.2014.179
Date Posted: 01 March 2022
This document has been peer reviewed.