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AbstractDO.05.02 Gene expression and Müller cell changes in experimental retinal vein occlusion in the rat Rehak M.1, Hollborn M.1, Yandiev Y.1, Pannicke T.2, Wiedemann P.1, Bringmann A.1
1Klinik und Poliklinik für Augenheilkunde, 2Paul-Flechsig-Institut für Hirnforschung, Universität Leipzig Objective: In a rat model of retinal vein occlusion, we determined the changes in the gene expression in the neural retina and pigment epithelium (RPE) of factors implicated in the development / resolution of edema. Further we investigated alterations of the potassium and water transport across the Müller cell membrane.
Methods: In one eye of adult Long-Evans rats, retinal veins near the optic nerve head were photocoagulated using a blue-green argon laser (parameters, 1.0 s, 50 microns, 50-100 mW). The untreated eyes served as controls. The eyes were enucleated one and three days after laser treatment, and the mRNA levels of VEGF-A, PEDF, Kir 4.1, Aquaporin-1 and -4 were determined with real-time PCR. The osmotic swelling of Müller cells was analyzed in retinal slices, and the potassium currents of isolated cells were recorded with the patch-clamp method.
Results: In the neural retina, the expression of VEGF was significantly (P<0.05) upregulated one day after experimental vein occlusion, and returned to the control level after three days. In contrast, the expression of VEGF was not altered in the RPE. PEDF was significantly (P<0.001) upregulated in the neural retina and RPE three days after vein occlusion. Kir4.1 and aquaporins were downregulated in both tissues one and three days after vein occlusion. Müller cells displayed a decrease in their potassium currents and an altered distribution of the Kir4.1 protein. A swelling of Müller cells under hypoosmotic stress was observed in occluded but not in control retinas.
Conclusions: Retinal branch vein occlusion results in a rapid transient increase in the expression of VEGF and a delayed increase in the expression of PEDF. The downregulation of Kir4.1 and aquaporins as well as the osmotic swelling of the Müller cells suggests an impairment in the retinal ion and water homeostasis that may contribute to the development of retinal edema and neuronal degeneration.
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