It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Proliferative vitreoretinopathy (PVR) with rhegmatogenous retinal detachment (RRD) is a complex inflammatory ocular disease. Statins are widely used cholesterol-lowering drugs with putative anti-inflammatory properties. In this study, we have explored their efficacy in controlling post-surgical PVR formation. Simvastatin (SIM), atorvastatin (ATV), or rosuvastatin (RSV) were added to cultures of human retinal pigment epithelial cells (ARPE-19) prior to exposure with the bacterial lipopolysaccharide (LPS), and the production of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) was examined using an enzyme-linked immunosorbent assay. In addition, the concentrations of simvastatin, atorvastatin, rosuvastatin, and their metabolites were measured from the vitreal samples of 20 patients undergoing vitrectomy (16 of them receiving oral statin therapy) using an ultra-performance liquid chromatography-tandem mass spectrometer technique. All statins alleviated LPS-induced inflammation at 5 µM concentration in the ARPE-19 cell cultures. Statin levels in the vitreous samples ranged from 6 to 316 pg/mL (ca. 0.1–7 M−10). Vitreal statin concentrations were similar to the typical steady-state unbound statin concentrations in plasma, indicating that only the unbound drug distributes from the blood circulation into the vitreous. Pharmacokinetic simulations of the intravitreal delivery of statins indicate that the measured clinical statin concentrations could be maintained with existing drug delivery technologies for months. Our results suggest that intravitreal statin therapy may have the potential in alleviating the risk of post-surgical PVR.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 University of Eastern Finland, School of Pharmacy, Faculty of Health Sciences, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490)
2 University of Helsinki, Department of Ophthalmology, Unit of Vitreoretinal Surgery, Helsinki University Central Hospital, and Individualized Drug Therapy Research Program, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)
3 University of Helsinki, School of Pharmacy, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071)
4 University of Eastern Finland, School of Pharmacy, Faculty of Health Sciences, Kuopio, Finland (GRID:grid.9668.1) (ISNI:0000 0001 0726 2490); University of Helsinki, School of Pharmacy, Helsinki, Finland (GRID:grid.7737.4) (ISNI:0000 0004 0410 2071); St. Petersburg State University, Institute of Chemistry, Petergof, Russian Federation (GRID:grid.15447.33) (ISNI:0000 0001 2289 6897)