Recent advances in drug and nutrient transport across the blood-retinal barrier

References

• Hosoya K, Tomi M, Tachikawa M. Strategies for therapy of retinal diseases using systemic drug delivery: relevance of transporters at the blood-retinal barrier. Expert Opin Drug Delivery. 2011;8:1571–1587.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Tachikawa M. Inner blood-retinal barrier transporters: role of retinal drug delivery. Pharm Res. 2009;26:2055–2065.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Tachikawa M. The inner blood-retinal barrier. In: Cheng CY, Eds. Biology and regulation of blood tissue barriers. USA: Springer; 2013. p. 85–104.
   Google Scholar
• Bucolo C, Drago F, Salomone S. Ocular drug delivery: a clue from nanotechnology. Front Pharmacol. 2012;3:188.
   PubMed Web of Science ®Google Scholar
• Schnaudigel O. Die vitale farbung mit trypanblau an auge. Graefes Arch Clin Exp Ophthalmol. 1913;86:93–105.
   Google Scholar
• Cunha-Vaz JG. The blood-retinal barriers system. Basic concepts and clinical evaluation. Exp Eye Res. 2004;78:715–721.
   PubMed Web of Science ®Google Scholar
• Yang X, Chung JY, Rai U, et al. Cadherins in the retinal pigment epithelium (RPE) revisited: P-cadherin is the highly dominant cadherin expressed in human and mouse RPE in vivo. PLoS One. 2018;13:e0191279.
   PubMed Web of Science ®Google Scholar
• Economopoulou M, Hammer J, Wang F, et al. Expression, localization, and function of junctional adhesion molecule-C (JAM-C) in human retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2009;50:1454–1463.
   PubMed Web of Science ®Google Scholar
• Peng S, Wang SB, Singh D, et al. Claudin-3 and claudin-19 partially restore native phenotype to ARPE-19 cells via effects on tight junctions and gene expression. Exp Eye Res. 2016;151:179–189.
   PubMed Web of Science ®Google Scholar
• Kojima S, Rahner C, Peng S, et al. Claudin 5 is transiently expressed during the development of the retinal pigment epithelium. J Membr Biol. 2002;186:81–88.
   PubMed Web of Science ®Google Scholar
• Barar J, Asadi M, Mortazavi-Tabatabaei SA, et al. Ocular drug delivery; impact of in vitro cell culture models. J Ophthalmic Vis Res. 2009;4:238–252.
   PubMedGoogle Scholar
• Sonoda S, Spee C, Barron E, et al. A protocol for the culture and differentiation of highly polarized human retinal pigment epithelial cells. Nat Protoc. 2009;4:662–673.
   PubMed Web of Science ®Google Scholar
• Hu J, Bok D. A cell culture medium that supports the differentiation of human retinal pigment epithelium into functionally polarized monolayers. Mol Vis. 2001;7:14–19.
   PubMed Web of Science ®Google Scholar
• Tomi M, Hosoya K. The role of blood-ocular barrier transporters in retinal drug disposition: an overview. Expert Opin Drug Metab Toxicol. 2010;6:1111–1124.
   PubMed Web of Science ®Google Scholar
• Stewart PA, Tuor UI. Blood-eye barriers in the rat: correlation of ultrastructure with function. J Comp Neurol. 1994;340:566–576.
   PubMed Web of Science ®Google Scholar
• Zhang Z, Uchida Y, Hirano S, et al. Inner blood-retinal barrier dominantly expresses breast cancer resistance protein: comparative quantitative targeted absolute proteomics study of CNS barriers in pig. Mol Pharm. 2017;14:3729–3738.
   PubMedGoogle Scholar
• Kubo Y, Akanuma S, Hosoya K. Impact of SLC6A transporters in physiological taurine transport at the blood-retinal barrier and in the liver. Biol Pharm Bull. 2016;39:1903–1911.
   PubMed Web of Science ®Google Scholar
• Ohkura Y, Akanuma S, Tachikawa M, et al. Blood-to-retina transport of biotin via Na+-dependent multivitamin transporter (SMVT) at the inner blood-retinal barrier. Exp Eye Res. 2010;91:387–392.
   PubMed Web of Science ®Google Scholar
• Yamamoto A, Akanuma S, Tachikawa M, et al. Involvement of LAT1 and LAT2 in the high- and low-affinity transport of L-leucine in human retinal pigment epithelial cells (ARPE-19 cells). J Pharm Sci. 2010;99:2475–2482.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Kyoko H, Toyooka N, et al. Evaluation of amino acid-mustard transport as L-type amino acid transporter 1 (LAT1)-mediated alkylating agents. Biol Pharm Bull. 2008;31:2126–2130.
   PubMed Web of Science ®Google Scholar
• Tomi M, Mori M, Tachikawa M, et al. L-Type amino acid transporter 1-mediated L-leucine transport at the inner blood-retinal barrier. Invest Ophthalmol Vis Sci. 2005;46:2522–2530.
   PubMed Web of Science ®Google Scholar
• Tomi M, Hosoya K, Takanaga H, et al. Induction of xCT gene expression and L-cystine transport activity by diethyl maleate at the inner blood-retinal barrier. Invest Ophthalmol Vis Sci. 2002;43:774–779.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Saeki S, Terasaki T. Activation of carrier-mediated transport of L-cystine at the blood-brain and blood-retinal barriers in vivo. Microvasc Res. 2001;62:136–142.
   PubMed Web of Science ®Google Scholar
• Bridges CC, Kekuda R, Wang H, et al. Structure, function, and regulation of human cystine/glutamate transporter in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2001;42:47–54.
   PubMed Web of Science ®Google Scholar
• Tachikawa M, Murakami K, Martin PM, et al. Retinal transfer of nicotinate by H+-monocarboxylate transporter at the inner blood-retinal barrier. Microvasc Res. 2011;82:385–390.
   PubMed Web of Science ®Google Scholar
• Babu E, Ananth S, Veeranan-Karmegam R, et al. Transport via SLC5A8 (SMCT1) is obligatory for 2-oxothiazolidine-4-carboxylate to enhance glutathione production in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2011;52:5749–5757.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Kondo T, Tomi M, et al. MCT1-mediated transport of L-lactic acid at the inner blood-retinal barrier: a possible route for delivery of monocarboxylic acid drugs to the retina. Pharm Res. 2001;18:1669–1676.
   PubMed Web of Science ®Google Scholar
• Alm A, Törnquist P. Lactate transport through the blood-retinal and the blood-brain barrier in rats. Ophthalmic Res. 1985;17:181–184.
   PubMed Web of Science ®Google Scholar
• Gerhart DZ, Leino RL, Drewes LR. Distribution of monocarboxylate transporters MCT1 and MCT2 in rat retina. Neuroscience. 1999;92:367–375.
   PubMed Web of Science ®Google Scholar
• Philp NJ, Yoon H, Grollman EF. Monocarboxylate transporter MCT1 is located in the apical membrane and MCT3 in the basal membrane of rat RPE. Am J Physiol. 1998;274:R1824–8.
   PubMed Web of Science ®Google Scholar
• Nagase K, Tomi M, Tachikawa M, et al. Functional and molecular characterization of adenosine transport at the rat inner blood-retinal barrier. Biochim Biophys Acta. 2006;1758:13–19.
   PubMed Web of Science ®Google Scholar
• Akanuma S, Soutome T, Hisada E, et al. Na+-independent nucleoside transporters regulate adenosine and hypoxanthine levels in Müller cells and the inner blood-retinal barrier. Invest Ophthalmol Vis Sci. 2013;54:1469–1477.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Fujita K, Tachikawa M. Involvement of reduced folate carrier 1 in the inner blood-retinal barrier transport of methyltetrahydrofolate. Drug Metab Pharmacokinet. 2008;23:285–292.
   PubMed Web of Science ®Google Scholar
• Umapathy NS, Gnana-Prakasam JP, Martin PM, et al. Cloning and functional characterization of the proton-coupled electrogenic folate transporter and analysis of its expression in retinal cell types. Invest Ophthalmol Vis Sci. 2007;48:5299–5305.
   PubMed Web of Science ®Google Scholar
• Chancy CD, Kekuda R, Huang W, et al. Expression and differential polarization of the reduced-folate transporter-1 and the folate receptor alpha in mammalian retinal pigment epithelium. J Biol Chem. 2000;275:20676–20684.
   PubMed Web of Science ®Google Scholar
• Puchowicz MA, Xu K, Magness D, et al. Comparison of glucose influx and blood flow in retina and brain of diabetic rats. J Cereb Blood Flow Metab. 2004;24:449–457.
   PubMed Web of Science ®Google Scholar
• Takata K, Kasahara T, Kasahara M, et al. Ultracytochemical localization of the erythrocyte/HepG2-type glucose transporter (GLUT1) in cells of the blood-retinal barrier in the rat. Invest Ophthalmol Vis Sci. 1992;33:377–383.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Minamizono A, Katayama K, et al. Vitamin C transport in oxidized form across the rat blood-retinal barrier. Invest Ophthalmol Vis Sci. 2004;45:1232–1239.
   PubMed Web of Science ®Google Scholar
• Tachikawa M, Okamoto M, Hirose S, et al. Inner blood-retinal barrier mediates l-isomer-predominant transport of serine. J Pharm Sci. 2011;100:3892–3903.
   PubMed Web of Science ®Google Scholar
• Nakashima T, Tomi M, Katayama K, et al. Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier. J Neurochem. 2004;89:1454–1461.
   PubMed Web of Science ®Google Scholar
• Okamoto M, Akanuma S, Tachikawa M, et al. Characteristics of glycine transport across the inner blood-retinal barrier. Neurochem Int. 2009;55:789–795.
   PubMed Web of Science ®Google Scholar
• Nakauchi T, Ando A, Ueda-Yamada M, et al. Prevention of ornithine cytotoxicity by nonpolar side chain amino acids in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2003;44:5023–5028.
   PubMed Web of Science ®Google Scholar
• Kageyama T, Nakamura M, Matsuo A, et al. The 4F2hc/LAT1 complex transports L-DOPA across the blood-brain barrier. Brain Res. 2000;879:115–121.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Akanuma S, Hosoya K. Influx transport of cationic drug at the blood-retinal barrier: impact on the retinal delivery of neuroprotectants. Biol Pharm Bull. 2017;40:1139–1145.
   PubMed Web of Science ®Google Scholar
• Tega Y, Kubo Y, Yuzurihara C, et al. Carrier-mediated transport of nicotine across the inner blood-retinal barrier: involvement of a novel organic cation transporter driven by an outward H+-gradient. J Pharm Sci. 2015;104:3069–3075.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Tsuchiyama A, Shimizu Y, et al. Involvement of carrier-mediated transport in the retinal uptake of clonidine at the inner blood-retinal barrier. Mol Pharm. 2014;11:3747–3753.
   PubMedGoogle Scholar
• Kubo Y, Kusagawa Y, Tachikawa M, et al. Involvement of a novel organic cation transporter in verapamil transport across the inner blood-retinal barrier. Pharm Res. 2013;30:847–856.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Shimizu Y, Kusagawa Y, et al. Propranolol transport across the inner blood-retinal barrier: potential involvement of a novel organic cation transporter. J Pharm Sci. 2013;102:3332–3342.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Fukui E, Akanuma S, et al. Application of membrane permeability evaluated in in vitro analyses to estimate blood-retinal barrier permeability. J Pharm Sci. 2012;101:2596–2605.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Yamamoto A, Akanuma S, et al. Lipophilicity and transporter influence on blood-retinal barrier permeability: a comparison with blood-brain barrier permeability. Pharm Res. 2010;27:2715–2724.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Tomi M. Advances in the cell biology of transport via the inner blood-retinal barrier: establishment of cell lines and transport functions. Biol Pharm Bull. 2005;28:1–8.
   PubMed Web of Science ®Google Scholar
• Terasaki T, Hosoya K. Conditionally immortalized cell lines as a new in vitro model for the study of barrier functions. Biol Pharm Bull. 2001;24:111–118.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Tomi M, Ohtsuki S, et al. Conditionally immortalized retinal capillary endothelial cell lines (TR-iBRB) expressing differentiated endothelial cell functions derived from a transgenic rat. Exp Eye Res. 2001;72:163–172.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Yamamoto M, Matsunaga K, et al. Retina-to-blood transport of 1-methyl-4-phenylpyridinium involves carrier-mediated process at the blood-retinal barrier. J Pharm Sci. 2017;106:2583–2591.
   PubMed Web of Science ®Google Scholar
• Tomi M, Arai K, Tachikawa M, et al. Na+-independent choline transport in rat retinal capillary endothelial cells. Neurochem Res. 2007;32:1833–1842.
   PubMed Web of Science ®Google Scholar
• Shen J, Cross ST, Tang-Liu DD, et al. Evaluation of an immortalized retinal endothelial cell line as an in vitro model for drug transport studies across the blood-retinal barrier. Pharm Res. 2003;20:1357–1363.
   PubMed Web of Science ®Google Scholar
• Kennedy BG, Mangini NJ. P-glycoprotein expression in human retinal pigment epithelium. Mol Vis. 2002;8:422–430.
   PubMed Web of Science ®Google Scholar
• Tagami M, Kusuhara S, Honda S, et al. Expression of ATP-binding cassette transporters at the inner blood-retinal barrier in a neonatal mouse model of oxygen-induced retinopathy. Brain Res. 2009;1283:186–193.
   PubMed Web of Science ®Google Scholar
• Tachikawa M, Toki H, Tomi M, et al. Gene expression profiles of ATP-binding cassette transporter A and C subfamilies in mouse retinal vascular endothelial cells. Microvasc Res. 2008;75:68–72.
   PubMed Web of Science ®Google Scholar
• Asashima T, Hori S, Ohtsuki S, et al. ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells. Pharm Res. 2006;23:1235–1242.
   PubMed Web of Science ®Google Scholar
• Hosoya K, Makihara A, Tsujikawa Y, et al. Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine. J Pharmacol Exp Ther. 2009;329:87–93.
   PubMed Web of Science ®Google Scholar
• Katayama K, Ohshima Y, Tomi M, et al. Application of microdialysis to evaluate the efflux transport of estradiol 17-beta glucuronide across the rat blood-retinal barrier. J Neurosci Methods. 2006;156:249–256.
   PubMed Web of Science ®Google Scholar
• Tomi M, Hosoya K. Application of magnetically isolated rat retinal vascular endothelial cells for the determination of transporter gene expression levels at the inner blood-retinal barrier. J Neurochem. 2004;91:1244–1248.
   PubMed Web of Science ®Google Scholar
• Gao B, Wenzel A, Grimm C, et al. Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2002;43:510–514.
   PubMed Web of Science ®Google Scholar
• Tsuji A. Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems. NeuroRx. 2005;2:54–62.
   PubMedGoogle Scholar
• Tsuji A, Terasaki T, Takabatake Y, et al. P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 1992;51:1427–1437.
   PubMed Web of Science ®Google Scholar
• Kodan A, Yamaguchi T, Nakatsu T, et al. Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog. Proc Natl Acad Sci U S A. 2014;111:4049–4054.
   PubMed Web of Science ®Google Scholar
• Zhang T, Xiang CD, Gale D, et al. Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos. 2008;36:1300–1307.
   PubMed Web of Science ®Google Scholar
• Hornof M, Toropainen E, Urtti A. Cell culture models of the ocular barriers. Eur J Pharm Biopharm. 2005;60:207–225.
   PubMed Web of Science ®Google Scholar
• Schlingemann RO, Hofman P, Klooster J, et al. Ciliary muscle capillaries have blood-tissue barrier characteristics. Exp Eye Res. 1998;66:747–754.
   PubMed Web of Science ®Google Scholar
• Wu J, Zhang JJ, Koppel H, et al. P-glycoprotein regulates a volume-activated chloride current in bovine non-pigmented ciliary epithelial cells. J Physiol. 1996;491:743–755.
   PubMed Web of Science ®Google Scholar
• Toda R, Kawazu K, Oyabu M, et al. Comparison of drug permeabilities across the blood-retinal barrier, blood-aqueous humor barrier, and blood-brain barrier. J Pharm Sci. 2011;100:3904–3911.
   PubMed Web of Science ®Google Scholar
• Takeuchi T, Yoshitomi S, Higuchi T, et al. Establishment and characterization of the transformants stably-expressing MDR1 derived from various animal species in LLC-PK1. Pharm Res. 2006;23:1460–1472.
   PubMed Web of Science ®Google Scholar
• Regina A, Koman A, Piciotti M, et al. Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J Neurochem. 1998;71:705–715.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Goldstein KM, Paulman A, et al. Minor compensatory changes in SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats do not detract from their utility in the study of transporter-mediated pharmacokinetics. Drug Metab Dispos. 2013;41:1174–1178.
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Bedwell DW, Bao JQ, et al. Characterization of SAGE Mdr1a (P-gp), Bcrp, and Mrp2 knockout rats using loperamide, paclitaxel, sulfasalazine, and carboxydichlorofluorescein pharmacokinetics. Drug Metab Dispos. 2012;40:1825–1833.
   PubMed Web of Science ®Google Scholar
• Fujii S, Setoguchi C, Kawazu K, et al. Impact of P-glycoprotein on blood-retinal barrier permeability: comparison of blood-aqueous humor and blood-brain barrier using mdr1a knockout rats. Invest Ophthalmol Vis Sci. 2014;55:4650–4658.
   PubMed Web of Science ®Google Scholar
• Pardridge WM, Fierer G. Blood-brain barrier transport of butanol and water relative to N-isopropyl-p-iodoamphetamine as the internal reference. J Cereb Blood Flow Metab. 1985;2:275–281.
   Google Scholar
• Alm A, Törnquist P. The uptake index method applied to studies on the blood-retinal barrier I. A methodological study. Acta Physiol Scand. 1981;113:73–79.
   PubMedGoogle Scholar
• Alm A, Törnquist P, Mäepea O. The uptake index method applied to studies on the blood-retinal barrier. II. Transport of several hexoses by a common carrier. Acta Physiol Scand. 1981;113:81–84.
   PubMedGoogle Scholar
• Törnquist P, Alm A. Carrier-mediated transport of amino acids through the blood-retinal and the blood-brain barriers. Graefes Arch Clin Exp Ophthalmol. 1986;224:21–25.
   PubMed Web of Science ®Google Scholar
• Karlsson C, Mäepea O, Alm A. Choline transport through the blood-retinal and the blood-brain barrier in vivo. Acta Ophthalmol (Copenh). 1984;62:763–766.
   PubMed Web of Science ®Google Scholar
• Chapy H, Saubaméa B, Tournier N, et al. Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier. Br J Pharmacol. 2016;173:497–510.
   PubMed Web of Science ®Google Scholar
• Bauer M, Karch R, Tournier N, et al. Assessment of P-glycoprotein transport activity at the human blood-retina barrier with (R)-11C-verapamil PET. J Nucl. 2017;58:678–681.
   Google Scholar
• Han YH, Sweet DH, Hu DN, et al. Characterization of a novel cationic drug transporter in human retinal pigment epithelial cells. J Pharmacol Exp Ther. 2001;296:450–457.
   PubMed Web of Science ®Google Scholar
• Tachikawa M, Takeda Y, Tomi M, et al. Involvement of OCTN2 in the transport of acetyl-L-carnitine across the inner blood-retinal barrier. Invest Ophthalmol Vis Sci. 2010;51:430–436.
   PubMed Web of Science ®Google Scholar
• Kido Y, Tamai I, Ohnari A, et al. Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier. J Neurochem. 2001;79:959–969.
   PubMed Web of Science ®Google Scholar
• Ohashi R, Tamai I, Yabuuchi H, et al. Na+-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999;291:778–784.
   PubMed Web of Science ®Google Scholar
• Yabuuchi H, Tamai I, Nezu J, et al. Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther. 1999;289:768–773.
   PubMed Web of Science ®Google Scholar
• Kelly RA, Smith TW. Recognition and management of digitalis toxicity. Am J Cardiol. 1992;69:108G–18G.
   PubMed Web of Science ®Google Scholar
• Noe B, Hagenbuch B, Stieger B, et al. Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain. Proc Natl Acad Sci USA. 1997;94:10346–10350.
   PubMed Web of Science ®Google Scholar
• Gao B, Stieger B, Noe B, et al. Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. J Histochem Cytochem. 1999;47:1255–1263.
   PubMed Web of Science ®Google Scholar
• Akanuma S, Hirose S, Tachikawa M, et al. Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at the rat blood-retinal barrier. Fluids Barriers CNS. 2013;10:29.
   PubMedGoogle Scholar
• Shitara Y, Sugiyama D, Kusuhara H, et al. Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002;19:147–153.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Seko N, Usui T, et al. Lysosomal trapping is present in retinal capillary endothelial cells: insight into its influence on cationic drug transport at the inner blood–retinal barrier. Biol Pharm Bull. 2016;39:1319–1324.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Nakazawa A, Akanuma S, et al. Blood-to-retina transport of fluorescence-labeled verapamil at the blood-retinal barrier. Pharm Res. 2018;35:93.
   PubMed Web of Science ®Google Scholar
• Okura T, Hattori A, Takano Y, et al. Involvement of the pyrilamine transporter, a putative organic cation transporter, in blood-brain barrier transport of oxycodone. Drug Metab Dispos. 2008;36:2005–2013.
   PubMed Web of Science ®Google Scholar
• Yamazaki M, Terasaki T, Yoshioka K, et al. Carrier-mediated transport of H1-antagonist at the blood-brain barrier: a common transport system of H1-antagonists and lipophilic basic drugs. Pharm Res. 1994;11:1516–1518.
   PubMed Web of Science ®Google Scholar
• Yamazaki M, Terasaki T, Yoshioka K, et al. Carrier-mediated transport of H1-antagonist at the blood-brain barrier: mepyramine uptake into bovine brain capillary endothelial cells in primary monolayer cultures. Pharm Res. 1994;11:975–978.
   PubMed Web of Science ®Google Scholar
• Yamazaki M, Fukuoka H, Nagata O, et al. Transport mechanism of an H1-antagonist at the blood-brain barrier: transport mechanism of mepyramine using the carotid injection technique. Biol Pharm Bull. 1994;17:676–679.
   PubMed Web of Science ®Google Scholar
• Chapy H, André P, Declèves X, et al. A polyspecific drug/proton antiporter mediates diphenhydramine and clonidine transport at the mouse blood-retinal barrier. Br J Pharmacol. 2015;172:4714–4725.
   PubMed Web of Science ®Google Scholar
• Cunha-Vaz JG. The blood-ocular barriers: past, present, and future. Doc Ophthalmol. 1997;93:149–157.
   PubMed Web of Science ®Google Scholar
• Duvvuri S, Gandhi MD, Mitra AK. Effect of P-glycoprotein on the ocular disposition of a model substrate, quinidine. Curr Eye Res. 2003;27:345–353.
   PubMed Web of Science ®Google Scholar
• Gao B, Huber RD, Wenzel A. Localization of organic anion transporting polypeptides in the rat and human ciliary body epithelium. Exp Eye Res. 2005;80:61–72.
   PubMed Web of Science ®Google Scholar
• Hagenbuch B, Meier PJ. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch. 2004;447:653–665.
   PubMed Web of Science ®Google Scholar
• Rajan PD, Kekuda R, Chancy CD, et al. Expression of the extraneuronal monoamine transporter in RPE and neural retina. Curr Eye Res. 2000;20:195–204.
   PubMed Web of Science ®Google Scholar
• Yoneyama D, Shinozaki Y, Lu WL, et al. Involvement of system A in the retina-to-blood transport of L-proline across the inner blood-retinal barrier. Exp Eye Res. 2010;90:507–513.
   PubMed Web of Science ®Google Scholar
• Withrow C, Ashraf S, O’Leary T, et al. Effect of polyamine depletion on cone photoreceptors of the developing rabbit retina. Invest Ophthalmol Vis Sci. 2002;43:3081–3090.
   PubMed Web of Science ®Google Scholar
• Kaneko S, Ueda-Yamada M, Ando A, et al. Cytotoxic effect of spermine on retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007;48:455–463.
   PubMed Web of Science ®Google Scholar
• Guo X, Harada C, Namekata K, et al. Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis. Invest Ophthalmol Vis Sci. 2011;52:2696–2703.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Tomise A, Tsuchiyama A, et al. Involvement of the carrier-mediated process in the retina-to-blood transport of spermine at the inner blood-retinal barrier. Exp Eye Res. 2014;124:17–23.
   PubMed Web of Science ®Google Scholar
• Aouida M, Poulin R, Ramotar D. The human carnitine transporter SLC22A16 mediates high affinity uptake of the anticancer polyamine analogue bleomycin-A5. J Biol Chem. 2010;285:6275–6284.
   PubMed Web of Science ®Google Scholar
• Daigle ND, Carpentier GA, Frenette-Cotton R, et al. Molecular characterization of a human cation-Cl- cotransporter (SLC12A8A, CCC9A) that promotes polyamine and amino acid transport. J Cell Physiol. 2009;220:680–689.
   PubMed Web of Science ®Google Scholar
• Busch AE, Quester S, Ulzheimer JC, et al. Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996;271:32599–32604.
   PubMed Web of Science ®Google Scholar
• Tomi M, Terayama T, Isobe T, et al. Function and regulation of taurine transport at the inner blood-retinal barrier. Microvasc Res. 2007;73:100–106.
   PubMed Web of Science ®Google Scholar
• Burns RS, Chiueh CC, Markey SP, et al. A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA. 1983;80:4546–4550.
   PubMed Web of Science ®Google Scholar
• Cuenca N, Herrero MT, Angulo A, et al. Morphological impairments in retinal neurons of the scotopic visual pathway in a monkey model of Parkinson’s disease. J Comp Neurol. 2005;493:261–273.
   PubMed Web of Science ®Google Scholar
• Kekuda R, Prasad PD, Wu X, et al. Cloning and functional characterization of a potential-sensitive, polyspecific organic cation transporter (OCT3) most abundantly expressed in placenta. J Biol Chem. 1998;273:15971–15979.
   PubMed Web of Science ®Google Scholar
• Itagaki S, Ganapathy V, Ho HT, et al. Electrophysiological characterization of the polyspecific organic cation transporter plasma membrane monoamine transporter. Drug Metab Dispos. 2012;40:1138–1143.
   PubMed Web of Science ®Google Scholar
• André P, Saubaméa B, Cochois-Guégan V, et al. Transport of biogenic amine neurotransmitters at the mouse blood-retina and blood-brain barriers by uptake1 and uptake2. J Cereb Blood Flow Metab. 2012;32:1989–2001.
   PubMed Web of Science ®Google Scholar
• Wu X, Kekuda R, Huang W, et al. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. J Biol Chem. 1998;273:32776–32786.
   PubMed Web of Science ®Google Scholar
• Usui T, Nakazawa A, Okura T, et al. Histamine elimination from the cerebrospinal fluid across the blood-cerebrospinal fluid barrier: involvement of plasma membrane monoamine transporter (PMAT/SLC29A4). J Neurochem. 2016;139:408–418.
   PubMed Web of Science ®Google Scholar
• Duan H, Hu T, Foti RS, et al. Potent and selective inhibition of plasma membrane monoamine transporter by HIV protease inhibitors. Drug Metab Dispos. 2015;43:1773–1780.
   PubMedGoogle Scholar
• Wu KC, Lu YH, Peng YH, et al. Effects of lipopolysaccharide on the expression of plasma membrane monoamine transporter (PMAT) at the blood-brain barrier and its implications to the transport of neurotoxins. J Neurochem. 2015;135:1178–1188.
   PubMed Web of Science ®Google Scholar
• Duan H, Wang J. Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther. 2010;335:743–753.
   PubMed Web of Science ®Google Scholar
• Sugiyama D, Kusuhara H, Taniguchi H, et al. Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood-brain barrier: high affinity transporter for thyroxine. J Biol Chem. 2003;278:43489–43495.
   PubMed Web of Science ®Google Scholar
• Nakazawa T, Takahashi H, Nishijima K. Pitavastatin prevents NMDA-induced retinal ganglion cell death by suppressing leukocyte recruitment. J Neurochem. 2007;100:1018–1031.
   PubMed Web of Science ®Google Scholar
• Kawaji T, Inomata Y, Takano A. Pitavastatin: protection against neuronal retinal damage induced by ischemia-reperfusion injury in rats. Curr Eye Res. 2007;32:991–997.
   PubMed Web of Science ®Google Scholar
• Saheki A, Terasaki T, Tamai I, et al. In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharm Res. 1994;11:305–311.
   PubMed Web of Science ®Google Scholar
• Gordon B, Chang S, Kavanagh M, et al. The effects of lipid lowering on diabetic retinopathy. Am J Ophthalmol. 1991;112:385–391.
   PubMed Web of Science ®Google Scholar
• Kikuchi R, Kusuhara H, Abe T, et al. Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors across the blood-brain barrier. J Pharmacol Exp Ther. 2004;311:1147–1153.
   PubMed Web of Science ®Google Scholar
• Fujii S, Setoguchi C, Kawazu K, et al. Functional characterization of carrier-mediated transport of pravastatin across the blood-retinal barrier in rats. Drug Metab Dispos. 2015;43:1956–1959.
   PubMed Web of Science ®Google Scholar
• Pelis RM, Shahidullah M, Ghosh S, et al. Localization of multidrug resistance-associated protein 2 in the nonpigmented ciliary epithelium of the eye. J Pharmacol Exp Ther. 2009;329:479–485.
   PubMed Web of Science ®Google Scholar
• Uchida Y, Kamiie J, Ohtsuki S, et al. Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007;24:2281–2296.
   PubMed Web of Science ®Google Scholar
• Hirano M, Maeda K, Matsushima S, et al. Sugiyama Y Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol. 2005;68:800–807.
   PubMed Web of Science ®Google Scholar
• Yamazaki M, Akiyama S, Ni’inuma K, et al. Biliary excretion of pravastatin in rats: contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter. Drug Metab Dispos. 1997;25:1123–1129.
   PubMed Web of Science ®Google Scholar
• Kusuhara H, Sugiyama Y. Active efflux across the blood-brain barrier: role of the solute carrier family. NeuroRx. 2005;2:73–85.
   PubMedGoogle Scholar
• Ohtsuki S, Yamaguchi H, Asashima T, et al. Establishing a method to isolate rat brain capillary endothelial cells by magnetic cell sorting and dominant mRNA expression of multidrug resistance-associated protein 1 and 4 in highly purified rat brain capillary endothelial cells. Pharm Res. 2007;24:688–694.
   PubMed Web of Science ®Google Scholar
• Phatchawan A, Chutima S, Varanuj C, et al. Decreased renal organic anion transporter 3 expression in type 1 diabetic rats. Am J Med Sci. 2014;347:221–227.
   PubMed Web of Science ®Google Scholar
• Hasegawa Y, Kishimoto S, Shibatani N, et al. The disposition of pravastatin in a rat model of streptozotocin-induced diabetes and organic anion transporting polypeptide 2 and multidrug resistance-associated protein 2 expression in the liver. Biol Pharm Bull. 2010;33:153–156.
   PubMed Web of Science ®Google Scholar
• Cha SH, Sekine T, Fukushima JI, et al. Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001;59:1277–1286.
   PubMed Web of Science ®Google Scholar
• Chan T, Zhu L, Madigan MC, et al. Human organic anion transporting polypeptide 1A2 (OATP1A2) mediates cellular uptake of all-trans-retinol in human retinal pigmented epithelial cells. Br J Pharmacol. 2015;172:2343–2353.
   PubMed Web of Science ®Google Scholar
• Gao B, Vavricka SR, Meier PJ, et al. Differential cellular expression of organic anion transporting peptides OATP1A2 and OATP2B1 in the human retina and brain: implications for carrier-mediated transport of neuropeptides and neurosteriods in the CNS. Pflugers Arch. 2015;467:1481–1493.
   PubMed Web of Science ®Google Scholar
• Shirasaka Y, Suzuki K, Nakanishi T, et al. Intestinal absorption of HMG-CoA reductase inhibitor pravastatin mediated by organic anion transporting polypeptide. Pharm Res. 2010;27:2141–2149.
   PubMed Web of Science ®Google Scholar
• Takeda M, Noshiro R, Onozato ML, et al. Evidence for a role of human organic anion transporters in the muscular side effects of HMG-CoA reductase inhibitors. Eur J Pharmacol. 2004;483:133–138.
   PubMed Web of Science ®Google Scholar
• Yonezawa A, Inui K. Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol Asp Med. 2013;34:693–701.
   PubMed Web of Science ®Google Scholar
• Foraker AB, Khantwal CM, Swaan PW. Current perspectives on the cellular uptake and trafficking of riboflavin. Adv Drug Deliv Rev. 2003;55:1467–1483.
   PubMed Web of Science ®Google Scholar
• Powers HJ. Riboflavin (vitamin B-2) and health. Am J Clin Nutr. 2003;77:1352–1360.
   PubMed Web of Science ®Google Scholar
• Irinoda K, Sato S. Contribution to the ocular manifestation of riboflavin deficiency. Tohoku J Exp Med. 1954;61:93–104.
   PubMedGoogle Scholar
• Ganea E, Harding JJ. Glutathione-related enzymes and the eye. Curr Eye Res. 2006;31:1–11.
   PubMed Web of Science ®Google Scholar
• Batey DW, Eckhert CD. Analysis of flavins in ocular tissues of the rabbit. Invest Ophthalmol Vis Sci. 1991;32:1981–1985.
   PubMed Web of Science ®Google Scholar
• Kuratomi K, Kobayashi Y. Studies on the interactions between DNA and flavins. Biochim Biophys Acta. 1977;476:207–217.
   PubMedGoogle Scholar
• Kubo Y, Yahata S, Miki S, et al. Blood-to-retina transport of riboflavin via RFVTs at the inner blood-retinal barrier. Drug Metab Pharmacokinet. 2017;32:92–99.
   PubMed Web of Science ®Google Scholar
• Bosch AM, Abeling NG, Ijlst L, et al. Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment. J Inherit Metab Dis. 2011;34:159–164.
   PubMed Web of Science ®Google Scholar
• Yao Y, Yonezawa A, Yoshimatsu H, et al. Identification and comparative functional characterization of a new human riboflavin transporter hRFT3 expressed in the brain. J Nutr. 2010;140:1220–1226.
   PubMed Web of Science ®Google Scholar
• Fujimura M, Yamamoto S, Murata T, et al. Functional characteristics of the human ortholog of riboflavin transporter 2 and riboflavin-responsive expression of its rat ortholog in the small intestine indicate its involvement in riboflavin absorption. J Nutr. 2010;140:1722–1727.
   PubMed Web of Science ®Google Scholar
• Yonezawa A, Masuda S, Katsura T, et al. Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1. Am J Physiol Cell Physiol. 2008;295:632–641.
   Web of Science ®Google Scholar
• Said HM, Wang S, Ma TY. Mechanism of riboflavin uptake by cultured human retinal pigment epithelial ARPE-19 cells: possible regulation by an intracellular Ca2+-calmodulin-mediated pathway. J Physiol. 2005;566:369–377.
   PubMed Web of Science ®Google Scholar
• Bridges CC, Ola MS, Prasad PD, et al. Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells. Am J Physiol Cell Physiol. 2001;281:C1825–36.
   PubMed Web of Science ®Google Scholar
• Kaneko S, Ando A, Okuda-Ashitaka E, et al. Ornithine transport via cationic amino acid transporter-1 is involved in ornithine cytotoxicity in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci. 2007;48:464–471.
   PubMed Web of Science ®Google Scholar
• Shambaugh GE. III. Urea biosynthesis. I The urea cycle and relationships to the citric acid cycle. Am J Clin Nutr. 1977;30:2083–2087.
   PubMed Web of Science ®Google Scholar
• Elam RP. Morphological changes in adult males from resistance exercise and amino acid supplementation. J Sports Med Phys Fitness. 1988;28:35–39.
   PubMed Web of Science ®Google Scholar
• Müting D, Kalk JF, Klein CP. Long-term effectiveness of high-dosed ornithine-aspartate on urea synthesis rate and portal hypertension in human liver cirrhosis. Amino Acids. 1992;3:147–153.
   PubMedGoogle Scholar
• Peraino C, Bunville LG, Tahmisian TN. Chemical physical, and morphological properties of ornithine aminotransferase from rat liver. J Biol Chem. 1969;244:2241–2249.
   PubMed Web of Science ®Google Scholar
• Raina A, Jänne J. Biosynthesis of putrescine: characterization of ornithine decarboxylase from regenerating rat liver. Acta Chem Scand. 1968;22:2375–2378.
   PubMedGoogle Scholar
• Takki K, Simell O. Genetic aspects in gyrate atrophy of the choroid and retina with hyperornithinaemia. Br J Ophthalmol. 1974;58:907–916.
   PubMed Web of Science ®Google Scholar
• Takki K. Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol. 1974;58:3–23.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Obata A, Akanuma S, et al. Impact of cationic amino acid transporter 1 on blood-retinal barrier transport of L-ornithine. Invest Ophthalmol Vis Sci. 2015;56:5925–5932.
   PubMed Web of Science ®Google Scholar
• Tomi M, Kitade N, Hirose S, et al. Cationic amino acid transporter 1-mediated L-arginine transport at the inner blood-retinal barrier. J Neurochem. 2009;111:716–725.
   PubMed Web of Science ®Google Scholar
• Closs EI, Gräf P, Habermeier A, et al. Human cationic amino acid transporters hCAT-1 hCAT-2A, and hCAT-2B: three related carriers with distinct transport properties. Biochemistry. 1997;36:6462–6468.
   PubMed Web of Science ®Google Scholar
• Closs EI, Albritton LM, Kim JW, et al. Identification of a low affinity, high capacity transporter of cationic amino acids in mouse liver. J Biol Chem. 1993;268:7538–7544.
   PubMed Web of Science ®Google Scholar
• Saito T, Omura K, Hayasaka S, et al. Hyperornithinemia with gyrate atrophy of the choroid and retina: a disturbance in de novo formation of proline. Tohoku J Exp Med. 1981;135:395–402.
   PubMed Web of Science ®Google Scholar
• Angelo S, Irarrázabal C, Devés R. The binding specificity of amino acid transport system y+L in human erythrocytes is altered by monovalent cations. J Membr Biol. 1996;153:37–44.
   PubMed Web of Science ®Google Scholar
• Vékony N, Wolf S, Boissel JP, et al. Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues. Biochemistry. 2001;40:12387–12394.
   PubMed Web of Science ®Google Scholar
• Frayser R, Buse MG. Branched chain amino acid metabolism in the retina of diabetic rats. Diabetologia. 1978;14:171–176.
   PubMed Web of Science ®Google Scholar
• Hayasaka S, Kodama T, Ohira A. Retinal risks of high-dose ornithine supplements: a review. Br J Nutr. 2011;106:801–811.
   PubMed Web of Science ®Google Scholar
• Kaneko S, Okuda-Ashitaka E, Ando A, et al. Polyamines upregulate the mRNA expression of cationic amino acid transporter-1 in human retinal pigment epithelial cells. Am J Physiol Cell Physiol. 2007;293:C729–37.
   PubMed Web of Science ®Google Scholar
• Ansurudeen I, Sunkari VG, Grünler J, et al. Carnosine enhances diabetic wound healing in the db/db mouse model of type 2 diabetes. Amino Acids. 2012;43:127–134.
   PubMed Web of Science ®Google Scholar
• Nagai K, Niijima A, Yamano T, et al. Possible role of L-carnosine in the regulation of blood glucose through controlling autonomic nerves. Exp Biol Med (Maywood). 2003;228:1138–1145.
   PubMed Web of Science ®Google Scholar
• Nagai K, Suda T, Kawasaki K, et al. Action of carnosine and beta-alanine on wound healing. Surgery. 1986;100:815–821.
   PubMed Web of Science ®Google Scholar
• Boldyrev A, Koudinov A, Berezov T, et al. Amyloid-beta induced cell death is independent of free radicals. J Alzheimers Dis. 2004;6:633–638.
   PubMed Web of Science ®Google Scholar
• Babizhayev MA, Seguin MC, Gueyne J, et al. l-Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem J. 1994;304:509–516.
   PubMed Web of Science ®Google Scholar
• Pfister F, Riedl E, Wang Q, et al. Oral carnosine supplementation prevents vascular damage in experimental diabetic retinopathy. Cell Physiol Biochem. 2011;28:125–136.
   PubMed Web of Science ®Google Scholar
• Sauerhöfer S, Yuan G, Braun GS, et al. L-Carnosine, a substrate of carnosinase-1, influences glucose metabolism. Diabetes. 2007;56:2425–2432.
   PubMed Web of Science ®Google Scholar
• Margolis FL, Grillo M. Carnosine, homocarnosine and anserine in vertebrate retinas. Neurochem Int. 1984;6:207–209.
   PubMed Web of Science ®Google Scholar
• Panzanelli P, Cantino D, Sassòe-Pognetto M. Co-localization of carnosine and glutamate in photoreceptors and bipolar cells of the frog retina. Brain Res. 1997;758:143–152.
   PubMed Web of Science ®Google Scholar
• Atluri H, Anand BS, Patel J, et al. Mechanism of a model dipeptide transport across blood-ocular barriers following systemic administration. Exp Eye Res. 2004;78:815–822.
   PubMed Web of Science ®Google Scholar
• Daniel H, Kottra G. The proton oligopeptide cotransporter family SLC15 in physiology and pharmacology. Pflugers Arch. 2004;447:610–618.
   PubMed Web of Science ®Google Scholar
• Ocheltree SM, Keep RF, Shen H, et al. Preliminary investigation into the expression of proton-coupled oligopeptide transporters in neural retina and retinal pigment epithelium (RPE): lack of functional activity in RPE plasma membranes. Pharm Res. 2003;20:1364–1372.
   PubMed Web of Science ®Google Scholar
• Usui T, Kubo Y, Akanuma S, et al. β-Alanine and L-histidine transport across the inner blood-retinal barrier: potential involvement in L-carnosine supply. Exp Eye Res. 2013;113:135–142.
   PubMed Web of Science ®Google Scholar
• Kubo Y, Akanuma S, Hosoya K. The blood-retinal barrier and carnosine. In: Preedy VR, Ed. Imidazole dipeptides: chemistry, analysis, function and effects. UK: Royal Society of Chemistry; 2015. p. 528–547.
   Google Scholar
• Borden LA. GABA transporter heterogeneity: pharmacology and cellular localization. Neurochem Int. 1996;29:335–356.
   PubMed Web of Science ®Google Scholar
• Smith KE, Borden LA, Wang CH, et al. Cloning and expression of a high affinity taurine transporter from rat brain. Mol Pharmacol. 1992;42:563–569.
   PubMed Web of Science ®Google Scholar
• Tomi M, Tajima A, Tachikawa M, et al. Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta. 2008;1778:2138–2142.
   PubMed Web of Science ®Google Scholar
• Segawa H, Fukasawa Y, Miyamoto K, et al. Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J Biol Chem. 1999;274:19745–19751.
   PubMed Web of Science ®Google Scholar
• Kanai Y, Segawa H, Miyamoto K, et al. Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998;273:23629–23632.
   PubMed Web of Science ®Google Scholar
• Tiedje KE, Stevens K, Barnes S, et al. Beta-alanine as a small molecule neurotransmitter. Neurochem Int. 2010;57:177–188.
   PubMed Web of Science ®Google Scholar
• Akimov NP, Marshak DW, Frishman LJ, et al. Histamine reduces flash sensitivity of on ganglion cells in the primate retina. Invest Ophthalmol Vis Sci. 2010;51:3825–3834.
   PubMed Web of Science ®Google Scholar
• Barar J, Aghanejad A, Fathi M, et al. Advanced drug delivery and targeting technologies for the ocular diseases. Bioimpacts. 2016;6:49–67.
   PubMed Web of Science ®Google Scholar
• Nakhlband A, Barar J. Impacts of nanomedicines in ocular pharmacotherapy. Bioimpacts. 2011;1:7–22.
   PubMedGoogle Scholar
• Maeda T, Lee MJ, Palczewska G, et al. Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. J Biol Chem. 2013;288:34484–34493.
   PubMed Web of Science ®Google Scholar