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William Evans, Ramesh Periasamy, RAJI RAJESH LENIN, Rajashekhar Gangaraju; Adipose Stem Cell Therapy for Early Retinal Complications of Diabetes in the Ins2Akita Mouse. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4033. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy (DR) is the most common vascular complication in patients with long-standing diabetes, and is the leading cause of blindness in working-age adults. Early stage DR has been shown to involve neurovascular defects, including the breakdown of retinal barrier integrity driven by ischemia, inflammation and apoptosis. In this study, we hypothesized that CD140b enriched adipose stem cells (ASC) or the paracrine factors released by these stem cells could therapeutically rescue early stage DR features.
Heterozygous male Ins2Akita mice were intravitreally injected with CD140b+ ASC (1000cells/eye), conditioned media (CM, 20x, 1mL/eye) or saline at 24 weeks of age. Age matched C57BL/6J mice with saline injections served as controls. The mice were analyzed after one and 2-weeks post-treatment by Electroretinography, OCT and OKN. The RayBio® Membrane-Based Antibody Array assessed differences in human cytokines released by CD140b+ASC CM compared with CD140b- ASC CM.
Ins2Akita diabetic mice that received saline injection demonstrated significantly decreased b-wave amplitude, decreased visual acuity and increased need for contrast sensitivity compared to non-diabetic mice. On the other hand, diabetic mice that received ASC or CM injection demonstrated robust increase in b-wave amplitude; visual acuity and a decrease need for contrast sensitivity compared to saline treated Ins2Akita diabetic mice (n=7, p<0.05). OCT demonstrated preserved retinal architecture following ASC and CM treatment. Of the 80 proteins tested, 47 proteins remained unchanged (>0.5-<1.5 fold), 9 proteins downregulated (<0.5 fold) and 24 proteins upregulated (>1.5 fold) in CD140b+ASC compared to CD140b-ASC.
First observations of ASC and CM treatment are highly favorable in the treatment against the early retinal complications of diabetes in the Ins2Akita model. Possible beneficial proteins from ASC-CM that are implicated in the observed paracrine effects of ASC in the retina were identified. Future molecular and histological analysis studies are needed to confirm the beneficial effects of the stem cells in vivo. Long term studies will look into identifying complications of stem cell treatment, including potential rejection and need for reinjection.
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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