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A.N. Witmer, R. van Zijderveld, B.C. van Blijswijk, R.O. Schlingemann, Ocular Angiogenesis Group AMC; Constitutive Vascular Expression of VEGFR-2 in Iris of Non-diabetic and Diabetic Persons Explains Rubeosis Iridis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3914.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Fluorescein angiography of the iris of diabetic patients has demonstrated increased permeability and rubeosis iridis of blood vessels, mainly at the pupillary margin. Vascular endothelial growth factor-A (VEGF-A) is an important vasopermeability and angiogenic factor in diabetic retinopathy. To investigate a possible role of VEGF-A in human diabetic iridopathy, we studied permeability changes in relation to expression patterns of the VEGF receptors VEGFR-2 and VEGFR-3 in the anterior segment (AS) in diabetes. Methods: VEGFR-2 and VEGFR-3 were detected by immunohistochemical staining in the AS of eyes of 14 diabetic and 14 non-diabetic persons. Anti-CD31 was used to identify blood vessels and staining for the non-barrier endothelial antigen PAL-E to investigate microvascular permeability. The total amount of positive iris vessels was counted for each antibody. Results: In non-diabetic iris, 28% of total iris vessels showed PAL-E staining, 40% showed VEGFR-2 staining and only 6% showed VEGFR-3 staining. Staining for PAL-E and the VEGFRs was most marked in blood vessels at the pupillary margin. In diabetic iris, a significant increase in vascular PAL-E staining was found (65% of total vessel count, p= 0.02). VEGFR-2 and VEGFR-3 staining was marginally increased (46% of total vessel count, p= 0.55; 8% of total vessel count, p= 0.35, respectively). Conclusions: In line with previous work, the permeability of iris vessels is increased in diabetes. However, the expression of VEGFRs in diabetic AS remained unchanged, as compared to non-diabetic AS. In fact, in contrast to our previous findings of absent VEGFR-2 and VEGFR-3 expression in the non-diabetic retinal vasculature, these receptors are constitutively expressed in the normal human iris, especially at the pupillary margin. This suggests a high sensitivity of the iris vasculature to VEGFs at this particular site, leading to the rapid induction of vascular leakage and rubeosis when VEGF-A is upregulated in the eye in ischemic retinopathies.
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