Dataset Information

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

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 Lactobacillus paracasei (LP), adult diabetic eNOS^-/- and Akita mice were orally gavaged with either 1 × 10⁹ 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.

SUBMITTER: Verma A

PROVIDER: S-EPMC7735952 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Verma Amrisha A Zhu Ping P Xu Kang K Du Tao T Liao Shengquan S Liang Zhibing Z Raizada Mohan K MK Li Qiuhong Q

Translational vision science & technology 20201214 13

<h4>Purpose</h4>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 ...[more]

PMID: 33344064

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Dataset Information

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

Purpose

Methods

Results

Conclusions

Translational relevance

Publications

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

Similar Datasets

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