Vasoregression in incipient diabetic retinopathy. Angiopoietin-2 dependency and the effect of erythropoietin and carnosine treatment

PhD ceremony: Mr. F. Pfister, 16.15 uur, Aula Academiegebouw, Broerstraat 5, Groningen

Dissertat: Vasoregression in incipient diabetic retinopathy. Angiopoietin-2 dependency and the effect of erythropoietin and carnosine treatment

Promotor(s): prof. G. Molema, prof. H.-P. Hammes

Faculty: Medical Sciences

The initial vascular changes of diabetic retinopathy (DR) are loss of capillary pericytes and vasoregression. The mechanisms causing diabetic vasoregression are complex and not completely understood. Recent findings indicated the importance of Ang-2 in DR, which was the subject of this thesis. The data show that overexpression of Ang-2 impairs pericyte recruitment and thereby enhances angiogenesis under physiological and pathological conditions. In diabetic and aging retinas, Ang-2 induces loss of retinal pericytes and vasoregression and we identified a new Ang-2 dependent mechanism of diabetic pericyte loss. The results described in this thesis indicate that the initiation and propagation of diabetic retinopathy strongly depends on firm pericyte coverage and the complex interplay between survival factors, such as VEGF, Hsp and other growth factors like the angiopoietins. Furthermore, we show that the neuroglial retina is a major target of early hyperglycemic damage and a key component in the pathogenesis of incipient DR. Understanding the interaction between neuroglial and vascular cells and the importance of factors released by these cells is of utmost importance for the development of novel and specific molecular drug targets with the potential to prevent or arrest the progression of DR.