Abstract
Purpose: :
We have previously identified l-DOPA as the ligand for OA1. We hypothesized that all forms of albinism have the same retinal phenotype since the albinism mutations all funnel into the same final common pathway - OA1 signaling (Lopez et al. PLoS Biology 2008). In this study, we sought to test this hypothesis both in vitro using albino model mouse RPE cultures and in vivo by l-DOPA supplementation during development.
Methods: :
We developed mouse RPE cultures from littermate OA1 -/y and OA1 +/y mice by adapting methods developed by Hu and Bok (Mol Vis. 2001). We also examined the use of supplemental l-DOPA to drive OA1 signaling in vivo of Tyr -/- pregnant dams to determine whether OA1 signaling could rescue retinal development in the pups.
Results: :
The mouse RPE cultures were polygonal, pigmented, and well differentiated. These cultured mouse RPE cells expressed both PEDF and CRALBP-1. In comparison of retinal PEDF levels, we found that retinas from OA1 -/y mice contained less PEDF than their OA1 competent littermate controls. In our in vivo studies, we observed an 18% increase in ganglion cells and a 10% increase in the ONL thickness in tyrosinase deficient mice supplemented with l-DOPA.
Conclusions: :
As our group has previously described, RPE pigmentation and PEDF are inter-related, regulated through an autocrine loop driven by OA1 signaling. The results from this study illustrate that OA1 and l-DOPA work together to facilitate retinal development, most likely through PEDF secretion.
Keywords: retinal pigment epithelium • signal transduction • development