2 - Biology of ocular transporters: efflux and influx transporters in the eye

Abstract

Transporters are membrane-bound proteins that play an important role in active transport of nutrients or xenobiotics. These transporters, in humans, play a significant role in the processes of drug absorption, distribution, metabolism and elimination. The presence of both efflux and influx transporters has been reported for various ocular tissues. The presence of efflux pumps on various ocular tissues has been shown to regulate the intracellular drug concentration needed to achieve therapeutic activity. Prominent members of efflux pumps include P-glycoprotein, multidrug resistance proteins and breast cancer resistance protein. These efflux pumps play an important role not only in extruding xenobiotics but also in maintaining the body’s homeostasis by their ubiquitous presence and capability to coordinate among themselves. On the other hand, influx transporters enable translocation of essential nutrients and xenobiotics across cell membranes. These include carriers for amino acids, peptides, vitamins, glucose, lactate and nucleoside/nucleobases. The most widely studied influx transporters for ocular drug delivery include peptide transporters, monocarboxylate transporters, organic cation transporters, organic anion transporters, the neutral and cationic amino acid transport system (B0’+), the organic anion transporting polypeptide family and sodium-dependent multivitamin transporter. In this chapter, the biology of efflux pumps and influx transporters with special emphasis on membrane topology, structural conformations, tissue localization and distribution, transport mechanisms, genomic properties and some important mutation sites are discussed in detail.