Purpose Aquaporin 4 (AQP4) is the most abundant water channel in the retina and participates in the formation of blood-retinal barrier (BRB). In several retinal pathologies accompanied by BRB dysfunction the expression of AQP4 is altered. In the present study, we investigated the effects of AQP4 deletion in the vascular retinal response to hypoxia. Methods We used wild type (WT) and AQP4 knockout (KO) mice. The retinal angiogenic response to hypoxia was studied in a mouse model of oxygen-induced retinopathy (OIR) using real time RT-PCR, Western blot, ELISA and immunohistochemistry. Results In WT mice, retinal levels of AQP4 were increased in response to hypoxia. In OIR mice, the BRB dysfunction was more pronounced in KO than in WT mice. BRB tight junction proteins, occludin, ZO-1 and JAM-C, were analyzed and significant alteration was found for JAM-C in KO mice, indicating a role for this protein in the observed dysfunctions. The formation of neovascular tufts, which are characteristic of OIR, was completely prevented in KO mice, possibly as a result of the decrease in hypoxia-induced up-regulation of VEGF mRNA and protein. Unexpectedly, this reduced increase in VEGF levels was paralleled by a dramatic increase in the activity of transcription factors which regulate VEGF expression indicating that in KO retinas mechanisms of VEGF transcription, such as promoter methylation, may be altered. Conclusion Together, the present results indicate a role for AQP4 in the formation of angiogenic processes in the retina and suggest that inhibiting AQP4 function may be a strategy to reduce pathologic angiogenesis in proliferative retinopathies.

Aquaporin 4 is required to induce retinal angiogenesis in a mouse model of oxygen-induced retinopathy / JOURNAL TOOLS Get New Content Alerts Get RSS feed Save to My Profile Get Sample Copy Recommend to Your Librarian JOURNAL MENU Journal Home FIND ISSUES Current Issue All Issues FIND ARTICLES Early View Editors' Choice Most Accessed GET ACCESS Subscribe / Renew FOR CONTRIBUTORS OnlineOpen Author Guidelines Submit an Article ABOUT THIS JOURNAL Society Information News Overview Editorial Board Permissions Advertise Contact SPECIAL FEATURES Special Issue on Glaucoma Wiley Job Network Custom Copy Jobs OnlineOpen F006 You have free access to this content Aquaporin 4 is required to induce retinal angiogenesis in a mouse model of oxygen-induced retinopathy M DAL MONTE; GP NICCHIA; M CAMMALLERI; IA FRIGERI; I FORNACIARI; F PISANI; P BAGNOLI; SVELTO M. - In: ACTA OPHTHALMOLOGICA. - ISSN 1755-3768. - 92:s253(2014).

Aquaporin 4 is required to induce retinal angiogenesis in a mouse model of oxygen-induced retinopathy

NICCHIA, GRAZIA PAOLA;PISANI, FRANCESCO;SVELTO, Maria
2014

Abstract

Purpose Aquaporin 4 (AQP4) is the most abundant water channel in the retina and participates in the formation of blood-retinal barrier (BRB). In several retinal pathologies accompanied by BRB dysfunction the expression of AQP4 is altered. In the present study, we investigated the effects of AQP4 deletion in the vascular retinal response to hypoxia. Methods We used wild type (WT) and AQP4 knockout (KO) mice. The retinal angiogenic response to hypoxia was studied in a mouse model of oxygen-induced retinopathy (OIR) using real time RT-PCR, Western blot, ELISA and immunohistochemistry. Results In WT mice, retinal levels of AQP4 were increased in response to hypoxia. In OIR mice, the BRB dysfunction was more pronounced in KO than in WT mice. BRB tight junction proteins, occludin, ZO-1 and JAM-C, were analyzed and significant alteration was found for JAM-C in KO mice, indicating a role for this protein in the observed dysfunctions. The formation of neovascular tufts, which are characteristic of OIR, was completely prevented in KO mice, possibly as a result of the decrease in hypoxia-induced up-regulation of VEGF mRNA and protein. Unexpectedly, this reduced increase in VEGF levels was paralleled by a dramatic increase in the activity of transcription factors which regulate VEGF expression indicating that in KO retinas mechanisms of VEGF transcription, such as promoter methylation, may be altered. Conclusion Together, the present results indicate a role for AQP4 in the formation of angiogenic processes in the retina and suggest that inhibiting AQP4 function may be a strategy to reduce pathologic angiogenesis in proliferative retinopathies.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/95238
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