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A Maminishkis, S Jalickee, SS Miller; Somatostatin (SST14) Enhances Retinal Reattachment of Experimentally Produced Subretinal Space (SRS) Blebs In Vivo . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4541.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: SST14 is a ubiquitous regulatory peptide that activates G-protein coupled receptors, and stimulates cAMP and Ca2+ - induced changes in a myriad of channels, antiporters, phosphatases, and other signaling pathways. ERG C-wave amplitude is altered by SST14 (Zalutsky, et al., 1990) and SST receptors (SSTR) have been localized at various sites in mammalian retinas, including the apical membrane of the RPE (Van Hagen et al., 2000). We tested the ability of SST14 to activate apical membrane receptors, and increase fluid transport from retina to choroid across bovine RPE in vitro and rat RPE in vivo. Methods: In vitro measurements were made using a previously developed capacitance probe technique in a modified Ussing chamber, to simultaneously record net fluid transport (JV), transepithelial potential (TEP), and resistance (RT). Experimental SRS blebs were produced in an in vivo rat model and fluid clearance rates from bleb to choroid were assessed under control and experimental conditions. SRS blebs were produced in anesthetized adult LE rats by injecting 2-3 µl of isotonic Ringer's solution between the retina and RPE under visual control. Drug injections were made either into the vitreous or into the bleb. The time course of bleb size change was recorded with a CCD camera. Volume changes were estimated by measuring the cross-sectional area of the bleb and by assuming an ellipsoid hemisphere with symmetrical minor axis. Results: In bovine RPE monolayers, in vitro, 500 nM apical SST14 increased TEP and decreased RT and more than doubled net fluid absorption (n = 6). Others have localized the receptor (SSTR2A) for this regulatory peptide to the apical membrane of human RPE. Given the remarkable clinical observation using an SST analogue in a patient with macular edema (Kuijpers et al., 1998), and our in vitro results, we tested the ability of SST14 to remove fluid from an experimental bleb in the rat model. Vitreous injection of SST14 removed 2-3 µl of fluid in 40 min from the retinal bleb (n =4). Conclusion: Activation of apical membrane SST receptors increases fluid absorption across bovine RPE in vitro and rat RPE in vivo suggesting that this peptide or its synthetic analogues could be useful in promoting retinal re-attachment.
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