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P.D. Senanayake, S. Miura, S. Karnik, J.G. Hollyfield; Angiotensin II and its Receptor Subtypes in the Human Eye . Invest. Ophthalmol. Vis. Sci. 2003;44(13):436.
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Purpose: To evaluate the distribution of Angiotensin II (Ang II) and its receptors in human ocular tissues. Methods: Donor eyes were obtained from the Cleveland Eye Bank within 12 hours of postmortem dissected on a chilled tray and the tissues were stored at -80?C. Ang II receptors were characterized and quantified in optic nerve, RPE-choroid complex, retina and ciliary body-iris by competitive membrane binding assays using Ang II, [Sar1 Ile 8] Ang II, and the subtype specific antagonists DUP 753 (AT1 -specific) and PD123319 (AT2-specific). Ang II in optic nerve, RPE-choroid complex, retina, vitreous, and ciliary body-iris was extracted with chilled HCL-Ethanol and concentrated using Water’s C18 Sep-Paks. Ang II was quantified by RIA. Results: Ang II receptors were present in the four tissues studied: retina,12.1 ± 0.3; RPE-Choroid complex, 6.6 ± 1.1; optic nerve, 3.4 ± 0.1; ciliary body-iris, 2.20 ± 0.4 fmol/mg protein (mean ± se; n=3). In the ciliary body-iris the receptors were exclusively AT1, however in the other tissues, both AT1 and AT2 were present. In the retina AT1 was predominant, in the RPE-choroid complex, the percentage of AT1 was higher than AT2. In the optic nerve, the percentage of AT1 and AT2 was comparable. The highest levels of Ang II were in the optic nerve, ranging from 8 to 819 pg/g (n=12, median 174). Vitreous had the lowest levels ,ranging from 3-32 pg/ml (n=27, median 9), The retina (1-367 pg/g, n=19.median =123), RPE-choroid complex (9-271 pg/g, n=12.median = 43), and ciliary body-iris (5-179 pg/g, n=11,median =44), had comparable levels. Conclusions: High levels of Ang II and Ang receptors are present in the vascularized ocular tissues. The variability in the levels of Ang II within each tissue may be a reflection of the heterogeneity of peptide expression and/or the accompanying therapeutic regimens. Local Ang II may be involved in blood supply and/or pathological processes such as neovascularization in diabetic retinopathy.
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