Effect of systemic immunosuppression and BM‐MSC allotransplantation in retinal functionality and RGC population

Abstract

AbstractPurposeBone marrow mesenchymal stem cell (BM‐MSC) transplant is widely studied in preclinical models because of their potential neuroprotective properties. In the clinic, allotransplants are combined with systemic immunosuppressive treatments to improve transplantation outcomes. We purposed to carry out a comparative functional and histological study to find out the role of immunosuppression after BM‐MSC allotransplantation in retina.Methods20,000 BM‐MSC from donor eGFP‐C57BL/6J mice were intravitreally injected into recipient BALB/c mice. Animals were divided in two groups (n=5/each). One group was immunosuppressed right after the BM‐MSC injection with oral cyclosporine in water (100 mg/ml) and a daily intraperitoneal injection of cortisone (1.6 mg/kg), whereas the other group was kept w/o immunosuppression as control. Electroretinograms were performed before and 5 days and 21 days after the BM‐MSC graft. Animals were perfused, and flat mounted retinas analyzed at 21 days. Brn3a+ retinal ganglion cells (RGC) were automatically quantified, and their spatial distribution analyzed with isodensity maps.ResultsBM‐MSC allotransplant alone causes a significant decrease (40%) of the positive scotopic threshold response (pSTR, RGC function) at 21 days compared to baseline. In the immunosuppressed group, retinal functionality was further impaired as most of the electroretinogram waves (pSTR, rod response, a and b waves, and photopic wave) drastically decreased at 5 days compared to allotransplant alone. This functionality was partially recovered at 21 days. In spite of the functional impairment, the population of RGC was not affected in any group.ConclusionsIn allogeneic BM‐MSC transplants, immunosuppression has a negative effect on retinal function.