June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Genetically modified probiotics for oral delivery of Angiotensin-(1-7) confers protection against diabetic complications
Author Affiliations & Notes
  • Qiuhong Li
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Zhibing Liang
    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
  • Ping Zhu
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Tuhina Prasad
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Shenquan Liao
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Manoj Kulkarni
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Amrisha Verma
    Ophthalmology, University of Florida, Gainesville, Florida, United States
  • Mohan Raizada
    Functional Genomics & Physiology, University of Florida, Gainesville, Florida, United States
  • Footnotes
    Commercial Relationships   Qiuhong Li, None; Zhibing Liang, None; Kang Xu, None; Tao Du, None; Ping Zhu, None; Tuhina Prasad, None; Shenquan Liao, None; Manoj Kulkarni, None; Amrisha Verma, None; Mohan Raizada , 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, 4049. doi:
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      Qiuhong Li, Zhibing Liang, Kang Xu, Tao Du, Ping Zhu, Tuhina Prasad, Shenquan Liao, Manoj Kulkarni, Amrisha Verma, Mohan Raizada; Genetically modified probiotics for oral delivery of Angiotensin-(1-7) confers protection against diabetic complications. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4049.

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

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Abstract

Purpose : Previous studies have established that activation of the members of the vasoprotective axis of the renin-angiotensin system [ACE2 or Angiotensin-(1-7) (Ang-(1-7)] prevents and arrests progression of diabetic retinopathy. The objective of present study was to generate a probiotic containing Ang-(1-7) and test the hypothesis that oral administration of such a probiotic would provide protection against diabetic retinopathy.

Methods : We genetically modified the commensal bacterium Lactobacillus paracasei (LP) to serve as a live vector for the oral delivery of Ang-(1-7) and investigated its therapeutic potential in attenuating diabetes and associated complications. Ang-(1-7) was expressed as a secreted fusion protein with a trans-epithelial carrier to allow uptake into circulation. The vector pTRKH3-ldh-SP-Ang-(1-7) or pTRKH3-ldh-GFP were introduced by electroporation into LP. Two-month old adult diabetic eNOS-/- mice induced by intraperitoneal injection of streptozotocin and Akita mice were orally gavaged every other day with 1x109 CFU of LP secreting Ang-(1-7) (LP-A), LP secreting GFP (LP-GFP), or LP alone for eight and twelve weeks respectively.

Results : Compared to age-matched untreated diabetic control animals, oral feeding of LP and LP-A significantly improved STZ-induced damage to insulin producing beta cells in pancreas in diabetic eNOS-/- mice. LP-A treatment also enhanced glucose tolerance, improved structure and morphology of islets and kidney, increased insulin expression in both diabetic eNOS-/- mice and Akita mice; and are associated with reduced retinal gliosis, inflammation, apoptotic neuronal cell death and loss of retinal vascular capillaries.

Conclusions : Oral administration of a genetically modified commensal bacterium that can secrete Ang-(1-7) provides protection against diabetes-induced tissue damage and diabetic retinopathy. Thus, LP-based delivery of Ang-(1-7) may hold important therapeutic potential for the treatment of diabetic complication.

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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