Abstract
Purpose: :
Diabetic retinopathy (DR) is traditionally considered as a microvascular complication in diabetic retinas . However, emerging evidences suggest that the loss of retinal neuron function and the death of retinal neurons are involved in DR. To determine whether Müller cell is a major cellular source of survival signals for photoreceptors in DR, we generated a mouse model of Müller cell-specific knockout for vascular endothelial growth factor receptor-2 (VEGFR2) . We then determined the effect of loss of VEGF signaling in Müller cells on their own survival and the survival of photoreceptors.
Methods: :
Diabetes was induced with streptozotocin. Retinal function was measured with electroretinography (ERG). Retinal morphology was assessed with hematoxylin & eosin (H&E) stained sections. The density of Müller cells and cone photoreceptors was evaluated with immunohistochemistry. Gene expression was analyzed with immunoblotting.
Results: :
While loss of VEGF signaling in Müller cells did not cause any apparent alteration in the retina under normal conditions, the conditional VEGFR2 knockout mice exhibited a significant loss of Müller cells, cones and rods, as well as both scotopic and photopic ERG amplitudes under diabetic conditions. Mechanistic studies regarding the diabetes-induced loss of photoreceptors are in progress.
Conclusions: :
Our results suggest that VEGF signaling is required for Müller cell survival and Müller cell is a major cellular source of survival signals for photoreceptors in DR.
Keywords: diabetic retinopathy • Muller cells • photoreceptors