Abstract
Purpose: :
Data concerning IgG metabolism and transport in the eye is scarse. However, recent new therapies with monoclonal antibodies, interpretation of the Goldmann-Wittmer coefficient (GWC) and the role of IgG in drusen warrant more studies to understand intraocular IgG processing. An important role for IgG remodeling is assigned to the neonatal Fc receptor (FcRn). Recently, we found that RPE cells express FcRn. Since the blood retina barrier consists not only of RPE cells but also of endothelial cells, we investigated expression and regulation of FcRn by human retinal endothelial cells (HRMVECs). Moreover, we studied FcRn expression by human immune cells which play an important role in inflammatory retinal diseases.
Methods: :
HRMVECs were purchased from Applied Cell Biology Research Institute (Kirkland, WA) and dermal endothelial cells, HMEC-1 cell lines were purchased from ATCC. Lymphocyte subsets were sorted from freshly harvested PBMCs from three healthy donors. FcRn and β2M mRNA levels were determined by RQ-PCR. Protein expression was determined by Western blot. Stimulation assays were performed with human TNF-alpha.
Results: :
Both HRMVEC and HMEC-1 cells express FcRn. However, FcRn expression in the retinal endothelium is downregulated by TNF-alpha, whereas FcRn expression in the dermal endothelium is upregulated by TNF-alpha. Both human B and T lymphocytes and monocytes express FcRn as well. Results of stimulation assays with human lymphocytes are pending.
Conclusions: :
HRMVEC cells express FcRn and this can be downregulated by TNF-alpha, similar to regulation in RPE cells. This is in contrast to FcRn regulation in periferal endothelial and epithelial cells. We also found FcRn expression in selected human immune cells, which may have implications for IgG remodelling in inflammatory retinal diseases. FcRn might well be an important factor in IgG transport over the blood retina barrier.
Keywords: immunomodulation/immunoregulation • immune tolerance/privilege • retinal pigment epithelium