Stem Cells are Mobilized from the Bone Marrow into the Peripheral Circulation in Response to Retinal Pigment Epithelium Damage—A Pathophysiological Attempt to Induce Endogenous Regeneration

Abstract

Purpose: Stem cell regeneration of damaged tissue has recently been reported in many different organs. Here, we investigated the mobilization of different stem/progenitor cell (SPC) populations into the peripheral blood (PB), their subsequent homing to the injured retina (IR) and contribution to its regeneration in a retinal pigment epithelium (RPE) damage model induced by sodium iodate (NaIO3).Methods: Mobilization of SPCs was evaluated by flow cytometry. SPCs distribution in IR was assessed using bone marrow (BM)-derived GFP+Lin− cells transplanted intravenously into NaIO3-treated C57Bl/6 mice. The quantity of the chemokine SDF-1 in PB and IR was measured by ELISA and qRT-PCR, respectively. Apoptosis (TUNEL assay), cell proliferation (PCNA analysis) as well as functional retinal activity (electroretinogram) were examined at several time points after NaIO3 administration.Results: Mobilization of SPCs along with the highest cell proliferation and massive apoptosis within IR were observed on the third day after NaIO3 administration. Similarly, donor GFP+Lin− cells were detected in the retina as soon as day 4 after NaIO3 injection. Plasma levels of SDF-1 did not differ significantly in mice exposed to NaIO3 compared to healthy controls, however mRNA for SDF-1 was overexpressed locally in IR. Functional retinal recovery was not achieved.Conclusion: Our study provides evidence that BM SPCs egress into PB and home to the injured retina, but are not capable of restoring its function. These results indicate that if the range of retinal destruction is profound, endogenous regeneration is ineffective and may ultimately require adjuvant therapeutic transplantation of specific SPCs subpopulations.