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Bokjun Ji, Jiyoung Lee, Daehan Lim, Hyung chan Kim, Hyewon Chung; Increased Wnt Modulators in Patients with Diabetic Macular Edema. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4294. doi: https://doi.org/.
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The Wnt pathway has been linked to numerous cellular processes, including angiogenesis, inflammation, and cellular survival. Its association with pathogenesis of diabetic retinopathy (DR) has been described. We previously showed that the levels of Wnt inhibitory factor 1 (WIF-1) and Dickkopf 3 (DKK-3) were significantly elevated in aqueous humor (AH) of neovascular age-related macular degeneration (nAMD) patients. In addition, the increased expression of WIF-1 and DKK-3 were correlated with the severity of outer retinal damage in nAMD. This study investigated the association between diabetic macular edema (DME) and levels of WIF-1 and DKK-3 in the AH of patients with DME and in the retina of diabetic animal models.
Twenty-eight eyes of twenty-three DME patients and 28 eyes of 28 age- and sex-matched controls were studied. AH WIF-1 and DKK-3 levels were measured by ELISA before the first intravitreal injection of bevacizumab. The levels of WIF-1 and DKK-3 and Wnt activation in the retina of Akita mice, a genetic model of type 1 diabetes, were measured by Western blot.
ELISA analysis showed increased levels of WIF-1 and DKK-3 in 28 patients with DME compared to the 28 controls (64.3±13.6 ng/mL vs. 22.2±90.3 ng/mL and 161.4±19.4 ng/mL vs. 101.6±38.3 ng/mL, respectively, both p < 0.0001). Western blot revealed that the levels of WIF-1, DKK-3, and active β-catenin were increased in the retina of Akita mice compared to control mice.
In the AH of DME patients and the retina of animal models, WIF-1 and DKK-3 were upregulated, possibly modulating the upregulation of Wnt signaling in DME. Wnt antagonists have been considered as potential treatments for DR. Our study suggests that WIF-1 and DKK-3 might have therapeutic potential as the treatment for DR.
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