Abstract
Purpose :
Corticosteroids are known as a risk factor for central serous chorioretinopathy (CSC), but the mechanism by which corticosteroids develop CSC remains unclear. Recently, a genome-wide association study reported an association of the SCL7A5 gene with CSC. SLC7A5 encodes an amino acid transporter LAT1 which is present in the retinal pigment epithelium (RPE). We investigated the transport activity for sodium fluorescein (Na-F) associated with LAT1 in cultured RPE (ARPE-19).
Methods :
ARPE-19 cells were grown to confluence. After withdrawing the serum, aldosterone (ALD) or hydrocortisone (HC) was added with several doses and incubated, and SLC7A5 gene expression was measured. The influx and efflux transports for Na-F were evaluated using a Transwell culture system. The role of LAT1 in these transports was examined by administering JPH203, a LAT1-specific inhibitor, and siRNA for SLC7A5.
Results :
SLC7A5 gene expression was upregulated by ALD and downregulated by HC in a dose-dependent manner. In the use of a dose that did not affect the gene expression of SLC7A5, the influx transport was significantly increased with ALD and HC by 2.2 and 4.3 times, respectively, compared with the control (P=0.025, P=2.45*10^-5), and these were significantly inhibited by JPH203 (P=0.0026, P=0.00098). The increase in efflux transport was 1.6 times and 1.5 times with ALD and HC, respectively, compared with the control (P=0.027, P=0.092), and these were significantly inhibited by JPH203 (P=0.03, P=0.0067). The siRNA for SLC7A5 also significantly inhibited influx transports of Na-F induced by ALD and HC (P=0.024, P=0.015) and an efflux transport induced by HC (P=0.045), but not for an efflux transport induced by ALD (P=0.086).
Conclusions :
The Na-F transports were increased by ALD and HC, and LAT1 is likely involved in these transports in ARPE-19 cells.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.