De. Ong et al., SYNTHESIS AND SECRETION OF RETINOL-BINDING PROTEIN AND TRANSTHYRETIN BY CULTURED RETINAL-PIGMENT EPITHELIUM, Biochemistry, 33(7), 1994, pp. 1835-1842
Recent studies indicate that the retinal pigment epithelium (RPE) may
serve as an extrahepatic source of retinol-binding protein (RBP) and t
ransthyretin (TTR) for the retina by virtue of the fact that this cell
layer is the exclusive retinal location for mRNA,coding for these pro
teins [Herbert, J., et al. (1991) Invest, Ophthalmol. Vis. Sci. 32, 30
2-309; Cavallaro, T., et al. (1990) Invest. Ophthalmol. Vis. Sci. 31,
497-501], although the proteins themselves are present in a variety of
retinal neurons. It is therefore necessary to determine whether these
mRNAs are translated and whether their translated products are secret
ed like hepatic RBP and TTR. Metabolic labeling of cultured bovine RPE
with [S-35] cysteine and [S-35] methionine and subsequent analysis of
newly synthesized proteins in the conditioned medium by affinity chro
matography, gel filtration, partial amino acid sequence analysis, and
autoradiography of electrophoretograms indicate that both RBP and TTR
are synthesized and secreted by the RPE. Moreover, for cells grown in
chambers with permeable supports, the predominant direction for secret
ion was into the apical medium. The mean apical:basal ratio after 72 h
of incubation was 9.2 for TTR and 4.5 for RBP. A function for these p
roteins in the neurosensory retina remains speculative. They could be
involved in the delivery of all-trans-retinol to amacrine and Muller c
ells as a precursor for retinoic acid, since these cells are known to
contain cellular retinoic acid binding protein [Gaur, V. P., et al. (1
990) Exp. Eye Res. 50, 505-511; Milam et al. (1990) J. Comp. Neurol. 2
96, 123-129]. A role in the visual cycle remains a possibility, althou
gh the evidence is stronger that this function may be fulfilled by int
erphotoreceptor retinoid-binding protein (IRBP). Finally, since these
proteins have been localized by immunocytochemistry to several neurona
l cell types in the retina, they may play a role in cell differentiati
on.