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J. Aranda, Y. Sassa, M. Prakash, P. Silva, L. Aiello, A. Kazlauskas; Diabetic Retinopathy Is Associated With Increased Vascular Stability. Invest. Ophthalmol. Vis. Sci. 2009;50(13):17.
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Increased levels of angiogenic agents (such as vascular endothelial growth factor, VEGF) in combination with low anti-angiogenic activity have been firmly associated with the development of proliferative diabetic retinopathy (PDR). Although anti-VEGF therapy for PDR is promising, treatment is not always effective. This strongly suggests that other aspects of vascular homeostasis are affected. We propose that PDR pathogenesis depends not only on the alteration of pro and anti-angiogenic growth factors, but also on decreased levels of vascular regression mediators.
Bovine retinal endothelial cells (BREC) were placed between two collagen layers and stimulated with VEGF. In response, the cells organized into tubes. Despite the daily addition of VEGF, the tubes spontaneously regressed within a day. We took advantage of this characteristic to test for the presence of agents able to modulate vascular regression. Vitreous of non-diabetic patients (no DM), diabetics without retinopathy (DM no DR), non-proliferative diabetic retinopathy patients (NPDR), proliferative diabetic retinopathy (PDR) specimens and quiescent PDR patients (QPDR) were added to preformed tubes, and the effect on spontaneous regression was evaluated.
Vitreous from non-angiogenic patients (no DM, DM no DR, NPDR and QPDR) promoted the regression of pre-formed tubes, whereas vitreous from PDR patients significantly delayed the regression of tubes.
Our results suggest that progression to PDR is associated with the loss of regression mediators that are normally present in non-angiogenic vitreous. Results from QPDR specimens imply that restoration of regression activity is associated with silenced angiogenesis. PDR development has been strongly associated with altered pro/anti-angiogenic balance. Our work suggests a more complex picture of PDR where not only is the angiogenic balance disrupted, but agents mediating the regression/stability of capillaries are also affected. Re-establishing the levels of regression agents may complement PDR therapy. We are currently focusing our efforts on identifying these agents.
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