Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous
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-surg...
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Nature Portfolio
2021-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-80127-1 |
| _version_ | 1818754194218156032 |
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| author | Yashavanthi Mysore Eva M. del Amo Sirpa Loukovaara Marja Hagström Arto Urtti Anu Kauppinen |
| author_facet | Yashavanthi Mysore Eva M. del Amo Sirpa Loukovaara Marja Hagström Arto Urtti Anu Kauppinen |
| author_sort | Yashavanthi Mysore |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-18T05:19:22Z |
| format | Article |
| id | doaj.art-95d06a7734c948688d69d89081f608d3 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T05:19:22Z |
| publishDate | 2021-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-95d06a7734c948688d69d89081f608d32022-12-21T21:19:42ZengNature PortfolioScientific Reports2045-23222021-01-0111111410.1038/s41598-020-80127-1Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreousYashavanthi Mysore0Eva M. del Amo1Sirpa Loukovaara2Marja Hagström3Arto Urtti4Anu Kauppinen5School of Pharmacy, Faculty of Health Sciences, University of Eastern FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern FinlandDepartment of Ophthalmology, Unit of Vitreoretinal Surgery, Helsinki University Central Hospital, and Individualized Drug Therapy Research Program, University of HelsinkiSchool of Pharmacy, University of HelsinkiSchool of Pharmacy, Faculty of Health Sciences, University of Eastern FinlandSchool of Pharmacy, Faculty of Health Sciences, University of Eastern FinlandAbstract 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.https://doi.org/10.1038/s41598-020-80127-1 |
| spellingShingle | Yashavanthi Mysore Eva M. del Amo Sirpa Loukovaara Marja Hagström Arto Urtti Anu Kauppinen Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous Scientific Reports |
| title | Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| title_full | Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| title_fullStr | Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| title_full_unstemmed | Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| title_short | Statins for the prevention of proliferative vitreoretinopathy: cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| title_sort | statins for the prevention of proliferative vitreoretinopathy cellular responses in cultured cells and clinical statin concentrations in the vitreous |
| url | https://doi.org/10.1038/s41598-020-80127-1 |
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