Diabetic retinopathy is a microangiopathy which is characterized by vasoregression due to the loss of pericytes and endothelial cells. Pericyte loss is the earliest vascular morphological change in non-proliferative diabetic retinopathy. Proliferative diabetic retinopathy occurs through retinal angiogenesis when new blood vessels grow out from the damaged vasculature. The newly formed blood vessels are leaky, bleed easily and thus obscure vision. Diabetic retinopathy is a major cause of blindness in developed countries.

The aim of our research group is to study the mechanisms underlying development of diabetic retinopathy and proliferative diabetic retinopathy and thus to provide novel intervention strategies for this disease.

We use

• in vivo, different transgenic mouse models in which we analyze for physiological retinal angiogenesis; hypoxia-induced proliferative retinopathy streptozotozin- and high fat-induced diabetic retinopathy.
• in vitro, primary vascular cells and retinal glia cells isolated either from transgenic mice or used for gene manipulation by transfection with gene-specific siRNA or transduced with viruses for gene overexpression.

Many angiogenic factors are essential in physiological and pathological retina, as well as proliferative diabetic retinopathy. Our previous study revealed that Angiopoetin-2 (Ang2) plays a substantial role in diabetic retinopathy, in both proliferative and non-proliferative stages. We use different animal models mimicking diabetic retinopathy as well as cultured cells mimicking diabetic cellular damages, to understand the signaling pathways involved in Ang2 regulation during glucose metabolism and angiogenic response in the retinal neurovascular unit.

Our current main focuses are:

• Signaling involved in protein GlcNAcylation and the Tie2-FOXO1-Ang2 cascade
• Caveolin1-mediated membrane trafficking in Tie2-FOXO1-Ang2 signaling
• Interaction of glucose and nucleotide metabolism and its role during Ang2 regulation in diabetes

1. Qiu Y, Zhao D, Butenschön VM, Bauer AT, Schneider SW, Skolnik EY, Hammes HP, Wieland T, Feng Y. Nucleoside diphosphate kinase B deficiency causes a diabetes-like vascular pathology via up-regulation of endothelial angiopoietin-2 in the retina. Acta Diabetol, 53:81-9, 2015.
2. Feng Y, Gross S, Wolf NM, Butenschön VM, Qiu Y, Devraj K, Liebner S, Kroll J, Skolnik EY, Hammes HP, Wieland T. Nucleoside diphosphate kinase B regulates angiogenesis through modulation of vascular endothelial growth factor receptor type 2 and endothelial adherens junction proteins. Arterioscler Thromb Vasc Biol,34: 2292-300, 2014.
3. Busch S, Wu L, Feng Y, Gretz N, Hoffmann S, Hammes HP. Alzheimer’s disease and retinal neurodegeneration share a consistent stress response of the neurovascular unit and the innate immunity systems. PLoS One, 9: e102013, 2014.
4. Busch S, Kannt A, Kolibabka M, Schlotterer A, Wang Q, Lin J, Feng Y, Hoffmann S, Gretz N, Hammes HP. Systemic treatment with erythropoietin protects the neurovascular unit in a rat model of retinal neurodegeneration. PLoS One, 11;9(7), 2014.
5. Feng Y, Wang Y, Yang Z, Wu L, Hoffmann S, Wieland T, Gretz N, Hammes HP. Chronic hyperglycemia inhibits vasoregression in a transgenic model of retinal degeneration. Acta Diabetol, 51: 211-8, 2014.
6. Carbajo-Lozoya J, Lutz S, Feng Y, Kroll J, Hammes HP, Wieland T. Angiotensin II modulates VEGF-driven angiogenesis by opposing effects of type 1 and type 2 receptor stimulation in the microvascular endothelium. Cell Signal, 24: 1261-9, 2012.
7. Feng Y, Busch S, Gretz N, Hoffmann S, Hammes HP. Crosstalk in the retinal neurovascular unit - lessons for the diabetic retina. Exp Clin Endocrinol Diabetes, 120:199-201, 2012.
8. Hammes HP, Feng Y, Pfister F, Brownlee M. Diabetic retinopathy: targeting vasoregression. Diabetes, 60: 9-16, 2011.
9. Feng Y, Wang Y, Li L, Wu L, Hoffmann S, Gretz N, Hammes HP. Gene expression profiling of vasoregression in the retina--involvement of microglial cells. PLoS One, 17;6:e16865, 2011.
10. Pfister F, Feng Y, vom Hagen F, Hoffmann S, Molema G, Hillebrands JL, Shani M, Deutsch U, Hammes HP. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes, 57: 2495-502, 2008.