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Odunayo Omolola Rotimi, Colin Green, Jie Zhang, Monica L Acosta, Ilva Rupenthal; Increased Connexin43 expression in a mouse model of advanced diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5430. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Diabetic retinopathy is a complication of diabetes that leads to vision loss in over 50% of diabetic patients. A novel transgenic mouse with enhanced expression of vascular endothelial growth factor (VEGF) and insulin deficiency (Akimba, Ins-/- VEGF+/-) has shown unique features of advanced diabetic retinopathy. Since other vascular disorders such as those resulting from spinal cord injury and retinal ischemia have shown increased Connexin43 levels and hemichannel opening, we hypothesize that the progression of vascular changes in Akimba mice is also associated with higher Connexin43 expression.
Retinal sections from 24 week old male Akimba and age-matched control (C57BL/6) mice (n=4) were immunohistochemically labelled for Connexin43 protein, astrocytosis and neovascularization using antibodies against Connexin43, glial fibrillary acidic protein (GFAP) and plasmalemma vesicular associated protein (PLVAP) in conjunction with the nuclear stain DAPI.
GFAP labelling was restricted to the ganglion cell layer in control mice but extended into all retinal layers in Akimba mice indicating Müller cell activation. There was a significant increase in both astrocytosis (p = 0.001) and overall Connexin43 levels (p = 0.002) as well as an upregulation of Connexin43 clusters on endothelial cells of new blood vessels in Akimba mice (p < 0.0001).
Astrocytosis and neovascularization correlated with increased Connexin43 expression in new blood vessels in the Akimba diabetic retinopathy model. These findings support a causal role of Connexin43 channels in the disease progression. Therefore, blocking Connexin43 hemichannels may be a novel therapeutic option to reduce vascular disruption in diabetic retinopathy.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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