Abstract
Purpose: :
We have shown that tyrosinase function influences retinal vascular regeneration and endothelial progenitor cell (EPC) recruitment to the retina after exposure to the oxygen induced retinopathy (OIR) model. We sought to determine whether tyrosinase function also influenced levels of EPCs in the bone marrow and blood.
Methods: :
B6(Cg)-Tyrc-2J/J ("B6(Cg)") is a commercially available strain of mice derived from the C57BL/6J strain with a spontaneous loss of function mutation in tyrosinase that has been bred to homozygosity. Pups from both strains were exposed 75% inspired oxygen for 120 hours, beginning on post-natal day 7 (P7). Mice were sacrificed 24 hours after return to normoxia and bone marrow and blood samples were taken for flow cytometry. Samples were also taken from age-matched control mice that had not been exposed to the OIR model. The proportions of DAPI-/CD45-/lo/CD34+/CD133+ EPCs were determined.
Results: :
Tyrosinase-deficient B6(Cg) mice were found to have more EPCs than C57BL/6J mice in both bone marrow (0.32% vs. 0.23%, p = 0.02) and blood samples (0.17% vs. 0.090%, p = 0.02). Mice of both strains had fewer EPCs in bone marrow samples after exposure to the OIR model (0.61% vs. 0.32%, p < 0.001 for B6(Cg) mice, and 0.30% vs. 0.23%, p < 0.001 for C57BL/6J mice). Both strains had slight increase in number of circulating EPCs in response to OIR exposure, but this difference did not reach statistical significance.
Conclusions: :
The greater level of EPC recruitment to the retina seen in B6(Cg) mice after exposure to the OIR model is associated with higher levels of EPCs in the bone marrow and blood. Further experiments are underway to determine the mechanism by which tyrosinase level influences EPC numbers. One possibility is that tyrosinase activity alters catecholamine levels, and these in turn influence EPC numbers.
Keywords: retinopathy of prematurity • genetics • regeneration