Angiotensin-(1-7) Expressed From Lactobacillus Bacteria Protect Diabetic Retina in Mice

Overview

Journal Transl Vis Sci Technol

Specialties Biomedical Engineering
Ophthalmology

Date 2020 Dec 21

PMID 33344064

Citations 11

Authors

Amrisha Verma

Ping Zhu

Kang Xu

Tao Du

Shengquan Liao

Zhibing Liang

Mohan K Raizada

Qiuhong Li

Affiliations

Soon will be listed here.

Abstract

Purpose: A multitude of animal studies substantiates the beneficial effects of Ang-(1-7), a peptide hormone in the protective axis of the renin angiotensin system, in diabetes and its associated complications including diabetic retinopathy (DR). However, the clinical application of Ang-(1-7) is limited due to unfavorable pharmacological properties. As emerging evidence implicates gut dysbiosis in pathogenesis of diabetes and supports beneficial effects of probiotics, we sought to develop probiotics-based expression and delivery system to enhance Ang-(1-7) and evaluate the efficacy of engineered probiotics expressing Ang-(1-7) in attenuation of DR in animal models.

Methods: Ang-(1-7) was expressed in the Lactobacillus species as a secreted fusion protein with a trans-epithelial carrier to allow uptake into circulation. To evaluate the effects of Ang-(1-7) expressed from (LP), adult diabetic eNOS and Akita mice were orally gavaged with either 1 × 10 CFU of LP secreting Ang-(1-7) (LP-A), LP alone or vehicle, 3 times/week, for 8 and 12 weeks, respectively.

Results: Ang-(1-7) is efficiently expressed from different Lactobacillus species and secreted into circulation in mice fed with LP-A. Oral administration of LP-A significantly reduced diabetes-induced loss of retinal vascular capillaries. LP-A treatment also prevented loss of retinal ganglion cells, and significantly decreased retinal inflammatory cytokine expression in both diabetic eNOS and Akita mice.

Conclusions: These results provide proof-of-concept for feasibility and efficacy of using engineered probiotic species as live vector for delivery of Ang-(1-7) with enhanced bioavailability.

Translational Relevance: Probiotics-based delivery of Ang-(1-7) may hold important therapeutic potential for the treatment of DR and other diabetic complications.

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