Transcriptional regulation of aquaporin-3 in human retinal pigment epithelial cells.

The expression of aquaporin (AQP) water channels may influence the development of retinal edema. We investigated the transcriptional regulation of AQP3 in cultured human retinal pigment epithelial (RPE) cells. As shown by RT-PCR and immunocytochemistry, cultured RPE cells express AQP3 mRNA and protein. The AQP3 mRNA level in RPE cells was elevated under the following conditions: chemical hypoxia induced by CoCl(2), hyperosmolarity induced by 100 mM NaCl, and upon stimulation of the cultures with PDGF, arachidonic acid, prostaglandin E(2), and blood serum, respectively. Chemical hypoxia increased AQP3 gene expression through MEK/ERK and JNK activation. The hyperosmolarity-, PDGF-, and serum-induced upregulation of AQP3 was prevented by inhibition of the phospholipase A(2), but not by inhibition of the cyclooxygenase. Triamcinolone acetonide prevented the upregulation of AQP3 induced by arachidonic acid and prostaglandin E(2), but not by the other factors tested. It is concluded that AQP3 is transcriptionally activated in RPE cells by various pathogenic factors involved in the development of retinal edema in situ. Activation of phospholipase A(2) is a critical factor which induces AQP3 in RPE cells.