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R. H. Rosa, Jr., G. W. Roddy, U. C. Krause, D. J. Prockop; Feasibility Study on Intravitreal and Subretinal Delivery of Adult Stem/Progenitor Cells (MSCs) for Retinal Repair. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3153.
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The current understanding of mesenchymal stem cell (MSC) biology indicates that MSCs are able to secrete anti-apoptotic, pro-growth, and/or anti-inflammatory proteins depending on the specific need of the injured tissue in order to preserve function. A limited number of in vivo studies with MSCs suggest a positive effect on the rescue of retinal degeneration. The mechanism of rescue effect, however, is not clearly established based on the published studies. We wish to determine the mechanism(s) by which photoreceptors and/or RPE are rescued by MSCs. Herein, we evaluated the feasibility of intravitreal and subretinal injections of MSCs in rodent and porcine experimental models.
After IACUC approval, adult Long Evans rats were sedated with a ketamine cocktail and redosed as needed and pigs (10-12 weeks old) were anesthetized with isoflurane for the entire length of the procedure. Pupil-dilating drops (tropicamide 0.5-1%, phenylephrine 2.5%) were paced in both eyes. Retinal fundus photography was performed with the RetCam II before and after the injections. Intravitreal injection of GFP-labeled mouse MSCs (10 µl/200,000 cells/PBS in rats; 50µl/1,000,000 cells/PBS in pigs; 30 gauge needle) was performed in the right eye followed by subretinal injection of mouse mesenchymal stem cells (2µl/40,000 cells/PBS in rats; 10µl/200,000 cells/PBS in pigs; 30 gauge needle) in the left eye using an operating microscope. The eyes were enucleated, and the animal subjects were euthanized. The eyes were examined by light and fluorescence microscopy.
Retinal fundus photography and histologic studies demonstrated the delivery of MSCs into the vitreous cavity and subretinal space in both rat and pig eyes. Intravitreal injections were performed without complications in both species. Acute complications with subretinal injections in both species included vitreous and subretinal hemorrhage and retinal perforation.
Intravitreal and subretinal delivery of MSCs is technically feasible in both small and large animal models. Potential complications with subretinal injections include intraocular hemorrhage and retinal perforation. Future studies will evaluate the potential benefit of high resolution ultrasound-guided microinjections of MSCs into the subretinal space and the mechanism(s) of rescue of retinal degeneration by MSCs.
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