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Effects of arteriolar constriction on retinal gene expression and Müller cell responses in a rat model of branch retinal vein occlusion

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Abstract

Background

To investigate the effect of induced arteriolar constriction (AC) on alterations in gene expression of factors implicated in the development of edema in branch retinal vein occlusion (BRVO).

Methods

In Brown-Norway rats, BRVO was induced by laser photocoagulation of the veins in one half of the retina. AC of the afferent arterioles was performed 30 min later. We then determined the expression of Vegfa, Vegfb, Pedf, Kir4.1, Aqp4, Aqp1, Il1ß, and Il6 with real-time polymerase chain reaction (RT-PCR) in the neuroretina and retinal pigment epithelium (RPE) after 1, 3, and 7 days. Immunostaining against GFAP, aquaporin (AQP)-4, and Kir4.1 was performed on days 1 and 3.

Results

BRVO resulted in transient upregulation of Vegfa in the neuroretina on day 1. The expressions of Kir4.1, AQP4, and AQP1 were downregulated, and Il1ß and Il6 were strongly upregulated, on days 1 and 3. The retinal distribution of GFAP and AQP4 proteins remained unaltered, while the Kir4.1 protein displayed redistribution from polarized to uniform retinal distribution. AC accelerated the restoration of downregulated Kir4.1, Aqp4, and Aqp1 in the RPE, of Kir4.1 in the neuroretina, and of upregulated Il6 in the neuroretina. AC did not influence the gliotic alterations of Müller cells and the redistribution of the Kir4.1 protein.

Conclusion

Constriction of the afferent artery in the BRVO region accelerated the restoration of potassium channels and Il6. These alterations may contribute to faster resorption of retinal edema, and may decrease the level of inflammation.

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Acknowledgments

This study was supported by grants from the Deutsche Forschungsgemeinschaft (KO 1547/6-1, GRK 1097/1). The authors wish to thank Ute Weinbrecht and Franziska Rickers for excellent technical assistance.

Conflict of interest

The authors declare that they have no conflict of interests to disclose. The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data upon request.

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Authors and Affiliations

  1. Department of Ophthalmology, University of Leipzig, Leipzig, Germany

    Patricia Köferl, Margrit Hollborn, Ianors Iandiev, Peter Wiedemann, Leon Kohen, Andreas Bringmann & Matus Rehak

  2. Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany

    Sladjana Dukic-Stefanovic

  3. Department of Ophtahlmology, Palacky University Olomouc, Olomouc, Czech Republic

    Jiri Rehak

  4. Helios Klinikum Aue, Aue, Germany

    Leon Kohen

  5. Department of Ophthalmology and Eye Hospital, Faculty of Medicine, University of Leipzig, Liebigstrasse 10-14, 04103, Leipzig, Germany

    Matus Rehak

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  1. Patricia Köferl
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  2. Margrit Hollborn
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Correspondence to Matus Rehak.

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Köferl, P., Hollborn, M., Rehak, J. et al. Effects of arteriolar constriction on retinal gene expression and Müller cell responses in a rat model of branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 252, 257–265 (2014). https://doi.org/10.1007/s00417-013-2532-z

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  • DOI: https://doi.org/10.1007/s00417-013-2532-z

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