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C. L. Decatur, R. Teeple, J. B. Stanton, A. D. Marmorstein, D. S. Rice, B. S. McKay; The OA1 Autocrine Loop: in vivo and in vitro. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1866.
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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.
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.
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.
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.
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