Diabetologie und Stoffwechsel 2007; 2 - P128
DOI: 10.1055/s-2007-982223

The role of ADAM 9/15 in mouse retinal development

Z Yang 1, F Pfister 1, F vom Hagen 1, J Tatsios 1, Y Feng 1, Y Wang 1, C Blobel 2, J Lin 1, HP Hammes 1
  • 15th Medical Department, University Hospital Mannheim, University of Heidelberg, Germany, Mannheim, Germany
  • 2Department of Cellular Biochemistry and Biophysics, Weill Medical college of Cornell University, New York, United States of America

Background: ADAM (a disintegrin and metalloprotease) family is important in diverse biologic processes such as cell adhesion and proteolytic shedding of cell surface receptors. Human ADAM15 (named metargidin) is the only one that has an argininel-glycine-aspartic acid (RGD) integrin-binding motif. However, the mouse and rat orthologues of ADAM15 lack an RGD sequence, but mouse ADAM15 can bind integrin α9β1. ADAM15 is strongly expressed in endothelial cell. Over expression ADAM15 showed to enhance cell-cell interaction and reduce cell migration. ADAM15-/- mice showed a 64% reduced neovascularization in an oxygen induced model of proliferative retinopathy. ADAM9-/- and ADAM9, 15-/- double knockout increase pathological neovascularization. However, the role of ADAM9 and 15 in angiogenesis is still unknown.

Objectives: To characterize the potential roles of ADAM9/15 in angiogenesis during development of mouse retina, we analyzed retinal morphometry.of ADAM9/15 double knockout mice and mixed-background 129/SVJ/C57BL/6J mice

Materials: The changes of morphometrics in retinal vessels were analyzed by using immunohistochemistry staining. Whole mount retinae of ADAM9, 15-/- and wild-type from postnatal day 0, 5, 10 and 15 (p0. p5, p10 and p15) were stained by isolectin B4 and sprouting tips, the outgrowth of retina, and diameter of capillaries, arterioles and venules were measured. Furthermore, GFAP expression of glial cells and pericyte specific expression of NG2 were detected.

Results: Our results showed that the diameter of capillary in ADAM9, 15-/- double knockout mice reduced about 8.5%, 17.5% and 22.4% at p5, p10 and p15 comparing to wild-type mouse, respectively. In contrast, ADAM9, 15-/- double knockout mice showed an increase in the arteriole diameter of 3.5%, 31.2% and 19.6% at p5, p10 and p15. Moreover, diameters of retinal venules were dilated 16.5% and 20% at p5 and p10 respectively. At p15 the dilatation of venules ameliorates. Interestingly, the double knockout mice showed more and longer sprouting tips than wild type mice at p0. However, the out growth of capillaries and retinae in WT-and KO-mice are similar from p5 to p15. Immunohistochemical analysis revealed that ADAM9, 15 double knockout affect the GFAP expression of glial cell and the abnormal coverage of pericyte in capillary.

Conclusion: ADAM9/15 play a critical role in controlling the retinal morphometrics and vessel remodeling.

Key words: ADAM9/15, angiogenesis and retinal capillary