Transporters and receptors in the posterior segment of the eye

Abstract

Treatment of vision-threatening retinal disorders is challenging because of physiological barriers. Entry of drug molecules to posterior ocular tissues from systemic and periocular sites is hampered by the presence of blood-retinal barriers (BRB). The BRB controls nutrient and xenobiotic access to posterior ocular tissues. Recent advancements in ophthalmic research have revealed the presence of a variety of transporters and receptors on BRB. These transport systems together play a key role in the infl ux of nutrients and the effl ux of metabolites and xenobiotics, and thereby help to maintain retinal homeostasis. The knowledge of expression and function of these transporters in BRB can help in the design of transporter-targeted prodrugs to improve posterior segment ocular drug delivery. This chapter provides insight into the role of transporters and receptors in maintaining the retinal milieu and proper functioning. In this chapter, current knowledge of transporters and receptors in posterior ocular tissues including glucose transporters, nucleoside transporters, creatine transporters, oligopeptide transporters, amino acid transporters, monocarboxylate transporters, organic anion and cation transporters, vitamin transporters, ATP-binding cassette transporters, folate receptor and 5

Retinaldehyde Dehydrogenase Inhibition-Related Adverse Outcome Pathway: Potential Risk of Retinoic Acid Synthesis Inhibition during Embryogenesis

“…A schematic representation of RALDH-mediated paracrine mechanisms of RA biosynthesis pathway from all-trans-retinol is presented in Figure 2. In serum, the all-trans-retinol is transiently bound to the secreted 21 kDa retinol-binding protein (RBP), which is a sole specific carrier synthesized within the liver, and RBP-retinol complex enters the cells via the membrane-attached STRA6 receptor, which is a 74 kDa multi-transmembrane domain protein [13,36,37]. Subsequently, the internalized retinol is either stored as retinyl esters or converted to RA [36,38].…”

“…However, since common animals have no retinol (vitamin A) synthesis mechanism, they obtain retinol in the forms of carotenoid and retinyl esters from their food, and RA is synthesized therefrom through the sequential process of RSP from the retinol content stored mainly in the liver, lungs, kidneys, and bone marrow [1]. The stored retinol is bound to retinol-binding protein 4 (RBP-4) in the serum and enters the cells via interaction with the STRA6 receptor [13]. Subsequently, the transferred retinol-RBP complex is metabolized to retinal through the reaction of retinol dehydrogenases (RODHs) or alcohol dehydrogenases (ADHs) and finally converted to RA by retinaldehyde (or retinal) dehydrogenase (RALDHs).…”

Computational Exploration of the Effects of Mutations on GABA Aminotransferase in GABA Aminotransferase Deficiency

“…GABA B receptors are metabotropic; upon activation by GABA, associated potassium channels are opened by G-protein coupled receptors, causing hyperpolarization and neuronal inhibition similar to that of GABA A receptors [ 6 ]. GABA’s function is halted after synaptic neurotransmission either by reuptake into presynaptic neurons or by absorption into glial cells through GABA transporters [ 7 ]. In glial cells, GABA is catabolized by GABA-AT (also called GABA-transaminase (GABA-T)), 4-aminobutyrate transaminase, and 4-aminobutyrate aminotransferase [ 8 , 9 ].…”

Lutein-Loaded, Biotin-Decorated Polymeric Nanoparticles Enhance Lutein Uptake in Retinal Cells

“…Formulation improvements include development of novel formulations such as suspensions, ointments, gels, nanoparticles, solutions, microemulsions, niosomes, liposomes, micelles, and others [ 1 , 2 , 17 ]. Transport of drugs, ions, and nutrients into and out of the ocular cell occurs mainly through transporters, receptors, and transmembrane proteins [ 19 , 20 , 21 ]. Transmembrane transporters/receptors are also involved in cellular processes such as absorption, distribution, and elimination of xenobiotics and nutrients [ 21 , 22 ].…”

“…Several transporters/receptors have been identified in the eye, which include glucose transporters, peptide transporters, amino acid transporters, nucleoside/nucleobase transporters, vitamin transporters, and nutrient receptors [ 21 , 22 ]. Various vitamin transporters have been characterized on the retinal epithelium which include folate, biotin, and ascorbic acid [ 20 , 22 ]. Transporter-mediated drug delivery can be achieved by conjugation of drug to a specific substrate/nutrient such as folic acid or biotin.…”