TY - JOUR
T1 - Dexamethasone intravitreal implant downregulates PDGFR-α and upregulates caveolin-1 in experimental branch retinal vein occlusion
AU - Cehofski, Lasse Jørgensen
AU - Kruse, Anders
AU - Magnusdottir, Sigriður Olga
AU - Alsing, Alexander Nørgård
AU - Nielsen, Jonas Ellegaard
AU - Kirkeby, Svend
AU - Honoré, Bent
AU - Vorum, Henrik
N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.
PY - 2018/6
Y1 - 2018/6
N2 - A dexamethasone (DEX) intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a DEX implant this study combined an experimental model of BRVO with proteomic techniques. In eight Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected into the right eye of each animal while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. DEX intervention reduced the retinal levels of platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor receptor 2 (VEGFR-2). DEX treatment resulted in increased levels of caveolin-1, peptidyl-prolyl cis-trans isomerase FKBP5 and transgelin. Changes in PDGFR-α and caveolin-1 were confirmed with immunohistochemistry. In BRVO treated with the DEX implant a strong reaction for caveolin-1 was observed in the innermost retinal layers. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier.
AB - A dexamethasone (DEX) intravitreal implant (OZURDEX) provides an effective treatment of inflammation secondary to branch retinal vein occlusion (BRVO). Retinal proteome changes which mediate the beneficial effects of the implant remain poorly understood. To study retinal proteome changes in BRVO following an intervention with a DEX implant this study combined an experimental model of BRVO with proteomic techniques. In eight Danish Landrace pigs experimental BRVO was induced in both eyes using argon laser. After inducing BRVO a DEX implant was injected into the right eye of each animal while the left control eye was given an identical injection without an implant. Fifteen days after BRVO and DEX implant intervention the retinas were excised and analyzed with tandem mass tag based mass spectrometry. A total of 26 significantly changed proteins were identified. DEX intervention reduced the retinal levels of platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor receptor 2 (VEGFR-2). DEX treatment resulted in increased levels of caveolin-1, peptidyl-prolyl cis-trans isomerase FKBP5 and transgelin. Changes in PDGFR-α and caveolin-1 were confirmed with immunohistochemistry. In BRVO treated with the DEX implant a strong reaction for caveolin-1 was observed in the innermost retinal layers. DEX implant intervention may inhibit PDGF signaling by decreasing the retinal level of PDGFR-α while an increased content of caveolin-1 may help maintain the integrity of the blood-retinal barrier.
U2 - 10.1016/j.exer.2018.02.029
DO - 10.1016/j.exer.2018.02.029
M3 - Journal article
C2 - 29505751
SN - 0014-4835
VL - 171
SP - 174
EP - 182
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -