Statins in rhegmatogenous retinal detachment are associated with low intravitreal angiopoietin-2, VEGF and MMP-2 levels, and improved visual acuity gain in vitrectomized patients

被引:16
作者
Tuuminen, Raimo [1 ]
Haukka, Jari [2 ]
Loukovaara, Sirpa [3 ]
机构
[1] Univ Helsinki, Cent Hosp, Dept Ophthalmol, FI-00290 Helsinki, Finland
[2] Univ Helsinki, Fac Med, Hjelt Inst, FI-00290 Helsinki, Finland
[3] Univ Helsinki, Cent Hosp, Dept Ophthalmol, Unit Vitreoretinal Surg, FI-00290 Helsinki, Finland
关键词
Angiopoietin-2; Inflammation; Rhegmatogenous retinal detachment; HMG-CoA reductase inhibitors; VEGF; Vitrectomy; PROLIFERATIVE VITREORETINOPATHY; GROWTH-FACTORS; EXPRESSION; RETINOPATHY; DEATH;
D O I
10.1007/s00417-014-2873-2
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
In rhegmatogenous retinal detachment (RRD), intravitreal growth factors and cytokines may compromise post-vitrectomy outcomes. Here, we analysed perioperative intravitreal protein levels of potent vasoactive, pro-inflammatory, and extracellular matrix-remodelling factors in RRD eyes of patients treated with statins and evaluated post-vitrectomy outcome in the same study eyes. Institutional, retrospective, observational study of 14 patients operated on for RRD while on statins compared to patients without statin medication (n = 82). Vitreous samples were subjected to protein measurements of angiopoietin (ANGPT)-1 and -2, transforming growth factor-beta 1, and vascular endothelial growth factor (VEGF) by ELISA, and of matrix metalloproteinase (MMP)-2 and -9 by gelatin zymography. A 1-month best-corrected visual acuity (BCVA) gain was modelled by Student's T-test and multivariate linear regression with concomitant perioperative medication. Cumulative 12-month revitrectomy frequency was modelled by Kaplan-Meier log-rank test. Intravitreal levels of ANGPT-2 (49.2 +/- 33.1 vs. 112.8 +/- 134.1 pg/ml, mean +/- SD, p < 0.001), VEGF (2.3 +/- 2.4 vs. 17.7 +/- 57.8 pg/ml, p = 0.021), and MMP-2 (1107.1 +/- 884.6 vs 1976.4 +/- 970.1 AU/ml, p = 0.005) in RRD eyes of patients treated with statins were lower than in non-statin-treated controls. Patients on statins had better 1-month BCVA improvement than did those not on statins (p = 0.022), with no difference in 1-year re-vitrectomy rates. Intravitreal levels of ANGPT-2, VEGF, factors involved in vascular permeability and inflammation, and activity of MMP-2, the factor connected with breakdown of basement membrane and fibroproliferation, were lower in RRD eyes of patients with statin treatment. At 1-month, postoperative BCVA gain was improved in statin-treated RRD eyes, suggesting that statin administration may be effective in preventing inflammation-related PVR formation.
引用
收藏
页码:1685 / 1693
页数:9
相关论文
共 20 条
[1]   HMG-CoA Reductase Inhibitors (Statin) Prevents Retinal Neovascularization in a Model of Oxygen-Induced Retinopathy [J].
Bartoli, Manuela ;
Al-Shabrawey, Mohamed ;
Labazi, Mohamed ;
Behzadian, M. Ali ;
Istanboli, Mohamed ;
El-Remessy, Azza B. ;
Caldwell, Robert W. ;
Marcus, Dennis M. ;
Caldwell, Ruth B. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2009, 50 (10) :4934-4940
[2]   Proliferative vitreoretinopathy - developments in adjunctive treatment and retinal pathology [J].
Charteris, DG ;
Sethi, CS ;
Lewis, GP ;
Fisher, SK .
EYE, 2002, 16 (04) :369-374
[3]   Angiopoietins: a link between angiogenesis and inflammation [J].
Fiedler, Ulrike ;
Augustin, Helimut G. .
TRENDS IN IMMUNOLOGY, 2006, 27 (12) :552-558
[4]   Pathophysiology of Proliferative Vitreoretinopathy in Retinal Detachment [J].
Garweg, Justus G. ;
Tappeiner, Christoph ;
Halberstadt, Markus .
SURVEY OF OPHTHALMOLOGY, 2013, 58 (04) :321-329
[5]   Angiopoietin-2 causes pericyte dropout in the normal retina - Evidence for involvement in diabetic retinopathy [J].
Hammes, HP ;
Lin, JH ;
Wagner, P ;
Feng, Y ;
vom Hagen, F ;
Krzizok, T ;
Renner, O ;
Breier, G ;
Brownlee, M ;
Deutsch, U .
DIABETES, 2004, 53 (04) :1104-1110
[6]   Profibrotic cytokines in aqueous humour correlate with aqueous flare in patients with rhegmatogenous retinal detachment [J].
Hoerster, Robert ;
Hermann, Manuel M. ;
Rosentreter, Andre ;
Muether, Philipp S. ;
Kirchhof, Bernd ;
Fauser, Sascha .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2013, 97 (04) :450-453
[7]   Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina [J].
Ko, Mei-Lan ;
Chen, Chau-Fong ;
Peng, Pai-Huei ;
Peng, Yi-Hao .
EXPERIMENTAL EYE RESEARCH, 2011, 93 (05) :580-585
[8]   Retinal detachment neuropathology and potential strategies for neuroprotection [J].
Kubay, OV ;
Charteris, DG ;
Newland, HS ;
Raymond, GL .
SURVEY OF OPHTHALMOLOGY, 2005, 50 (05) :463-475
[9]   Pleiotropic effects of statins [J].
Liao, JK ;
Laufs, U .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2005, 45 :89-118
[10]   Apoptosis and Other Cell Death Mechanisms after Retinal Detachment: Implications for Photoreceptor Rescue [J].
Lo, Amy C. Y. ;
Woo, Tiffany T. Y. ;
Wonsg, Raymond L. M. ;
Wong, David .
OPHTHALMOLOGICA, 2011, 226 :10-17