Incidence and outcome of mild cognitive impairment in a population-based prospective cohort

Abstract

Since there is paucity of information on solute transporters in human ocular tissues, the aim of this study was immunohistochemical and functional characterization of peptide transporters (PEPT), organic cation transporters (OCTs), neutral and basic amino acid transporters (ATB0,+), and monocarboxylate transporters (MCTs) in human ocular barriers. Immunohistochemical localization of transporters was achieved using 5-µm-thick paraffin-embedded sections of whole human eyes. In vitro transport studies were carried out across human cornea and sclera-choroid-retinal pigment epithelium (SCRPE) using a cassette of specific substrates in the presence and absence of inhibitors to determine the role of transporters in transtissue solute delivery. Immunohistochemistry showed the expression of PEPT-1, PEPT-2, ATB0,+, OCT-1, OCT-2, MCT-1, and MCT-3 in human ocular tissues. PEPT-1, PEPT-2, OCT-1, MCT-1, and ATB0,+ expression was evident in the cornea, conjunctiva, ciliary epithelium, and neural retina. Expression of PEPT-1, PEPT-2, and OCT-1 was evident in choroid tissue as well. OCT-2 expression could be seen in the corneal and conjunctival epithelia, whereas MCT-3 expression was confined to the RPE layer. OCT-2 expression was evident in conjunctival blood vessel walls, whereas PEPT-1, PEPT-2, and OCT-1 were expressed in the choroid. Preliminary transport studies indicated inward transport of Gly-Sar (PEPT substrate), 1-methyl-4-phenylpyridinium (MPP+) (OCT substrate), and l-tryptophan (ATB0,+ substrate) across cornea as well as SCRPE. For phenylacetic acid (MCT substrate), transporter-mediated inward transport across the cornea and outward transport across SCRPE were evident. Thus, PEPT, OCT, and ATB0,+ are influx transporters present in human ocular barriers, and they can potentially be used for transporter-guided retinal drug delivery after topical, transscleral, and systemic administrations.