One of the ABC transporters, P-glycoprotein (P-gp, also known as Mdr1 and Abcb1), is expressed in iris, ciliary muscle, and ciliary nonpigmented cells,
10–12 which are part of the BAB. Various SLC transporters, organic cation/carnitine transporter (OCTN) 1 (SLC22A4), OCTN2 (SLC22A5), organic cation transporter 1 (OCT1; SLC22A1), and organic anion transporter 3 (OAT3; SLC22A8) are expressed in the human iris-ciliary body,
12 and organic anion transporting polypeptides1a4 (oatp2; slco1a4), 1a5 (oatp3; slco1a5), and 1b2 (oatp4; slco1b2) are found in the rat ciliary body.
13 Furthermore, in the BRB, P-gp is localized in the luminal membrane of retinal capillary endothelial cells,
5,14,15 and in the apical and basal sides of the RPE.
15 The expression of SLC transporters, such as OCTNs, oatp families, and novel cationic transporters, also has been reported in the inner and/or outer BRB.
8 According to these reports,
14,15 the contribution of P-gp in the inner BRB is lower than that in the BBB; accordingly, Toda et al.
16 and Hosoya et al.
17 have reported that in rats, the P-gp function is less active in the BRB than in the BBB. In the rat genome, there are two paralogous genes encoding P-gp,
mdr1a and
mdr1b. Among most of the P-gp substrates that we tested in this study, including quinidine, digoxin, and verapamil, there were no differences between rat
mdr1a and
mdr1b in P-gp substrate recognition.
18 However,
mdr1a is the predominant form in the rat inner BRB
19 as well as the BBB,
20 although the predominant form in rat outer BRB and BAB still is unclear.