Abstract
Purpose: :
The interior of the eye is a pharmacological sanctuary to therapeutic drugs of clinical importance. Many of these drugs, including antivirals, antibiotics and chemotherapeutics are organic anions at physiological pH. Although it has been demonstrated that organic anions are cleared from the eye by a transport mediated process, the site(s) at which this occurs, and the transport proteins involved, are not well understood. Because the ciliary epithelium is a metabolically active tissue with a large transport capacity, it was hypothesized that organic anion transporters in the SLC22A, SLC13A and ABC families would be expressed in this tissue (with the expectation that they facilitate efflux of organic anions out of the eye).
Methods: :
Reverse transcription polymerase chain reaction was used to look for mRNA expression of organic anion transporters in a human ciliary body cDNA library and cDNA isolated from primary cultures of porcine non-pigmented epithelium. Complementary DNA isolated from human or porcine kidney was used as positive controls. Sequencing was used to confirm amplification of the specific sequences.
Results: :
mRNA corresponding to OAT1 (SLC22A6), MRP2 (ABCC2), MRP4 (ABCC4), and BCRP (ABCG2) were identified in the human ciliary body cDNA library. mRNA for the same transporters was found in primary cultures of porcine non-pigmented epithelium. MRP1 (ABCC1), NaDC1 (SLC13A2) and NaDC3 (SLC13A3) mRNA was not detected.
Conclusions: :
These data indicate that several organic anion transporters common to other barrier and excretory tissues are expressed in the ciliary epithelium. The ciliary epithelium, and specifically these transporters, may influence drug efficacy in the eye.
Keywords: ciliary body • ion transporters • pump/barrier function