Yoshito Fujiseki (1,3), Kyoko Omori (1), Koichiro Omori (2), Yoshito
Mikami (3), Junko Suzukawa (1), Gaku Okugawa (1), Masanobu Uyama (3) and
Chiyoko Inagaki (1,*)
Departments of (1) Pharmacology, (2) Physiology and (3) Ophthalmology, Kansai
Medical University, Moriguchi, Osaka 570-8506, Japan
(*) To whom correspondence should be addressed.
Abstract: We tried to detect natriuretic peptide (NP) receptor
(NPR-A and NPR-B) mRNAs in cultured rabbit retinal pigment epithelium (RPE)
cells and examined the regulation of their expression in relation to subretinal
fluid absorption or RPE cell proliferation. RPE cells from 2 - 4 passages
were grown to confluence on microporous membranes and analyzed for levels
of expression of receptor mRNAs by quantitative RT-PCR and Northern blotting.
The expression of NPR-B mRNA was approximately tenfold higher than that
of NPR-A mRNA. The expression of NPR-A mRNA was not affected by treatments
that may change subretinal fluid transport, while that of NPR-B mRNA was
inhibited by transmitters involved in light- and dark-adaptation such as
dopamine and melatonin. Expression of NPR-B mRNA was also suppressed by
platelet-derived growth factor and transforming growth factor-beta. Furthermore,
atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP), ligands
for NPR-A and B, respectively, inhibited the proliferation of RPE cells,
as analyzed by incorporation of [3H]thymidine. These findings
suggest that ANP may be involved in constitutive absorption of subretinal
fluid and that NPs form an important regulatory system of proliferation
in RPE cells.
Keywords: Retinal pigment epithelium (RPE), Atrial natriuretic peptide
(ANP), C-type natriuretic peptide (CNP), Natriuretic peptide receptor-A
(NPR-A), Natriuretic peptide receptor-B (NPR-B)