Safety and effects of intravitreal or subretinal injections of human bone marrow‐derived mononuclear cells to P23H‐1 and RCS rats

Abstract

AbstractPurposeTo determine the safety and effects of intravitreal or subretinal injections of human bone marrow‐derived mononuclear cells (HBMNCs) in two different rat models of hereditary photoreceptor (FR) degeneration.Methods21‐days‐old Homozygous P23H‐1 albino rats, Royal College of Surgeons (RCS) pigmented rats or control SD and PVG rats received one intravitreal injection or one subretinal injection of HBMNCs (5µl; 50,000 cells/µl). As controls, intact animals of P23H‐1, RCS, SD and PVG strains were used. All animals were immunosuppressed with oral cyclosporine and intraperitoneal dexamethasone and were processed 7, 15, 30 or 60 days after transplantation. The eyes were cross‐sectioned in a cryostat and the sections immunodetected to visualize HBMNCs (□‐human CD45), photoreceptors (□‐Recoverin), astrocytes and Müller cells (□‐GFAP), or microglial cells (□‐Iba‐1). Sections were examined under fluorescence and confocal microscopy to investigate retinal structure and photoreceptor cell survivalResultsIn HBMNCs treated eyes no macro or microscopic anomalies, tumours, necrosis, inflammation or infective phenomena were observed. In the intravitreally injected eyes, HBMNCs‐CD45+ were found in the vitreous and attached to the inner limiting membrane. In the eyes with subretinal injections, HBMNCs‐CD45+ were found forming a layer in the subretinal space. When compared to control animals, the transplanted eyes of P23H‐1 and RCS rats showed decreased GFAP expression, indicating a reduction of gliosis. However, we did not observe increased photoreceptor survival in dystrophic animals after transplantation.ConclusionsHBMNCs injection to the vitreous or subretinal space in immunosupresed rats lack adverse effects and in P23H‐1 and RCS rats decrease the retinal gliosis but do not elicit photoreceptor neuroprotective effects.