Oral delivery of ACE2/Ang-(1-7) bioencapsulated in plant cells protects against experimental uveitis and autoimmune uveoretinitis

Mol Ther. 2014 Dec;22(12):2069-2082. doi: 10.1038/mt.2014.179. Epub 2014 Sep 17.


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.

MeSH terms

  • Administration, Oral
  • Angiotensin I / administration & dosage*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Chloroplasts / genetics*
  • Chloroplasts / metabolism
  • Disease Models, Animal*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Peptide Fragments / administration & dosage*
  • Peptidyl-Dipeptidase A / administration & dosage*
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / metabolism*
  • Retinal Vasculitis
  • Retinitis / chemically induced
  • Retinitis / immunology
  • Retinitis / therapy*
  • Uveitis / chemically induced
  • Uveitis / immunology
  • Uveitis / therapy*


  • Peptide Fragments
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)