2008-05: The clinical importance of the neonatal Fc receptor in RPE
IgG levels in the vitreous are used to diagnose ocular infections (Goldmann-Witmer) and recently anti-VEGFs (Avastin, Lucentis) have been introduced to treat neovascular age related macular degeneration (ARMD). In the near future other immunoglobulin based biologicals will be injected in the eye. Monoclonal anti-TNF antibodies such as Remicade and Humira are promising candidates for local administration and also cytotoxic monoclonals like rituximab - for treating ocular lymphomas - are to be injected locally. However, knowledge about metabolism of IgG in the eye is scarce. Investigation of the metabolism and transport mechanisms of these antibodies is therefore warranted.
Mutations or polymorphisms of the FcRn gene may indicate a predisposition for ARMD. The fact that IgG is found in drusen and in retinal pigment epithelial (RPE) cells adjacent to drusen indicates a possible role for IgG and therefore the neonatal Fc receptor (FcRn) in the development of ARMD.
The aim of this study is to demonstrate that the FcRn functions as a transporter and protector for vitreous IgG and monoclonals (Avastin, Lucentis) and show that monoclonal therapeutic antibodies are transported over the RPE via the FcRn. 2) To investigate if polymorphisms or mutations in the FcRn gene or promoter are related to ARMD.