June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Oral delivery of Angiotensin-(1-7) bioencapsulated in plant cells protect against diabetes-induced retinopathy and other complications
Author Affiliations & Notes
  • Amrisha Verma
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Kang Xu
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Tao Du
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Manoj Kulkarni
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Ping Zhu
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Tuhina Prasad
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Henry Daniell
    Biochemistry and Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Qiuhong Li
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Footnotes
    Commercial Relationships   Amrisha Verma, None; Kang Xu, None; Tao Du, None; Manoj Kulkarni, None; Ping Zhu, None; Tuhina Prasad, None; Henry Daniell, None; Qiuhong Li, None
  • Footnotes
    Support  Supported in part by NIH grants EY021752, EY024564, American Diabetes Association, BrightFocus Foundation (QL) and NIH grant R01 HL102033 (MKR). Core facilities were supported by NEI grant P30 EY02172 and Research to Prevent Blindness to University of Florida.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5213. doi:
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      Amrisha Verma, Kang Xu, Tao Du, Manoj Kulkarni, Ping Zhu, Tuhina Prasad, Henry Daniell, Qiuhong Li; Oral delivery of Angiotensin-(1-7) bioencapsulated in plant cells protect against diabetes-induced retinopathy and other complications. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5213.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Our previous studies demonstrated that increased expression of Ang-(1-7), the key member of the vasoprotective axis of the renin angiotensin system (RAS), via AAV-mediated retinal gene delivery, reduced diabetes-induced retinal pathology, providing the proof-of-concept that enhancing this axis is a promising approach for treating patients with DR. In addition, enhanced expression of Ang-(1-7) also improves lipid and glucose metabolism, ameliorates insulin resistance and confers protection against a variety of pathological conditions. Thus an ideal strategy would be to enhance this axis both systemically and locally at target tissues. This study was aimed to test the hypothesis that oral delivery of Ang-(1-7) bioencapsulated in plant cells would confer protection against diabetes-induced retinopathy in animal models.

Methods : Ang-(1-7) peptide fused with non-toxic cholera toxin subunit B (CTB) was expressed in plant chloroplasts. Diabetic eNOS-/- mice induced by STZ and Akita mice were orally gavaged with wild-type or Ang-(1-7) leaf materials three times/week, for eight weeks.

Results : Increased level of Ang-(1-7) was observed in circulation and retina after oral administration of CTB- Ang-(1-7). Ang (1-7) leaf material treatment significantly improved the glucose tolerance and insulin sensitivity in diabetic eNOS-/- and Akita mice, increased insulin expression of the pancreatic islets compared to control groups (untreated or treated with wild-type leaf material). Ang (1-7) leaf material treatment also significantly reduced apoptotic cell death in kidney, as well as diabetes- induced RGC loss, gliosis and microglial cell activation, expression of inflammatory cytokines in diabetic retina, improved mitochondrial function and prevented retinal endothelial capillary loss.

Conclusions : Our results demonstrate that orally administered Ang-(1-7) bioencapsulated in plant cells can be efficiently delivered into circulation and target tissues; orally administered bioencapsulated Ang-(1-7) not only mitigated diabetic retinopathy, but also improved systemic parameters and other diabetic complications, thus enhancing the protective axis of RAS by oral delivery of Ang-(1–7) bioencapsulated in plant cells provide an innovative, highly efficient and cost-effective therapeutic strategy for treating diabetes and diabetic complications.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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