Abstract

FR.14.08

Cellular and molecular basis of diabetic retinopathy

Hammes H.-P., Vom Hagen F., Feng Y.
5. Medizinische Klinik, Universitätsklinikum Mannheim

The two most characteristic lesions of incipient diabetic retinopathy are increased vascular permeability and progressive vascular occlusion. The loss of pericytes and endothelial cells are part of the generalized vasoregression induced by chronic hyperglycemia, while focal endothelial proliferation and capillary thrombosis are already signs of a response to injury. Microaneurysms have been perceived as early abortive attempts of neovascularization. According to recent findings, a particular role of retinal neuroglia in the pathogenesis of diabetic retinopathy is suggested. Retinal Müller cells are important in the maintenance of vision, in the protection against oxidative stress, the integrity of the blood retinal barrier, and the supply of vascular cells with survival factors. In animals, Müller cells transdifferentiate during incipient retinopathy as indicated by de-novo expression of GFAP. Upregulation of small heat shock proteins and ROS-dependent repair enzymes further indicate glial activation. Among several others, the modulation of vascular response to hyperglycemic injury involves the angiopoietin-Tie system. While the agonistic ligand angiopoietin 1 mediates vessel maturation, resistance to stress, and tightening of the blood retinal barrier, the natural antagonist angiopoietin 2 sensitizes the vessel to repair or regression. Ang-2 is involved in pericyte loss and, in cooperation with VEGF, in neovascularization. Müller cells are important in the microenvironmental supply and regulation of Ang-2. The molecular mechanisms of transcriptional regulation of Ang-2 have been deciphered demonstrating that intracellular methylglyoxal-type AGE are involved. Together, the novel data have led to a better understanding in the biochemistry and cell biology of diabetic retinopathy, providing the rationale for more specific treatments.

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