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)