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Amirfarbod Yazdanyar, Pengfei Zhang, Christian Dolf, whitney Cary, Missy Pham, Jan Nolta, Robert J Zawadzki, Nicholas Marsh-Armstrong, Susanna S Park; Protective effects of Intravitreal injection of human CD34+ stem cells from bone marrow on diabetic retinopathy in a murine model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):979.
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© ARVO (1962-2015); The Authors (2016-present)
Human CD34+ stem cells have been shown to home into damaged retinal vasculature following intravitreal injection. However, their therapeutic effects are yet to be determined. The goal of this study is to investigate whether intravitreal injection of human CD34+ stem cells from bone marrow has protective effect on progression of retinal vascular damage in a murine model of diabetic retinopathy
Streptozotocin-induced diabetic mice (C57BL/6J) were used as murine model for diabetic retinopathy. Continuous systemic immunosuppression was achieved for the study duration by subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection. Human CD34+ cells were isolated from bone marrow aspirate by positive selection using magnetic beads. The isolated cells were labelled with enhanced green fluorescent protein (EGFP). The right eyes of immunosuppressed diabetic mice received intravitreal injection of 50,000 EGFP-labeled CD34+ cells (n= 12) or saline (n=12). The eyes were imaged at 4 weeks following intravitreal injection using simultaneous multimodal in vivo retinal imaging which combined scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), phase-variance OCT angiography and fluorescein angiography. After imaging, the eye was removed and immunohistochemical analysis was performed on the retinal flat mount to evaluate the retinal vasculature.
Fluorescein and OCT angiography showed retinal microvascular changes consistent with early diabetic retinopathy in all mice. Multimodal in vivo imaging showed the presence of human CD34+ cells from bone marrow in the vitreous, along the retinal vasculature and retinal surface. Immunohistochemical analysis of the retinal vasculature on retinal flat mount using a vascular specific marker showed preservation of the retinal vasculature in CD34+ stem cell injected eyes when compared with PBS injected control eyes.
Multimodal in vivo imaging in a murine model of diabetic retinopathy demonstrated long-term retinal homing and integration of human CD34+ stem cells from bone marrow following a single intravitreal injection. Immunohistochemical analysis showed preservation of the retinal vasculature following intravitreal CD34+ stem cells treatment in these eyes with diabetic retinopathy.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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