title: Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis.
abstract: 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.
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Pollob K
authors.initials: PK
authors.lastname: Shil
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Kwang-Chul
authors.initials: KC
authors.lastname: Kwon
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA.
authors.forename: Amrisha
authors.initials: A
authors.lastname: Verma
authors.affiliation: Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address: hdaniell@upenn.edu.
authors.forename: Henry
authors.initials: H
authors.lastname: Daniell
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida, USA. Electronic address: qli@ufl.edu.
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000803:Angiotensin I / Q000008:administration & dosage*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002736:Chloroplasts / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage*; D007703:Peptidyl-Dipeptidase A / Q000008:administration & dosage*; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism*; D031300:Retinal Vasculitis; D012173:Retinitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology / Q000628:therapy*
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)