Ultrastructural defects of the basal lamina and interstitial ECM around ICAP-1–deficient blood vessels are associated with increased permeability to small molecules. (A) Transmission electron micrographs of retinal capillaries showing dilation of ICAP-1−/− capillary compared with ICAP+/+. Bar, 1 µm. Enlargements of the yellow square show that basal lamina (BL) around ICAP-1−/− capillary present zones of multilayering due to dispersion of the dense matter and zones of accumulation of matter in spots (arrows). EC, endothelial cell; P, pericyte. Bar, 0.5 µm. (B) Arrows indicate zones of tearing of the basal lamina around an ICAP-1−/− venule. SMC, smooth muscle cell. Bar, 1 µm. (C) Fenestrated choroidal capillaries showing multilayering of the basal lamina (BL) juxtaposed to EC and enlargement of the interstitial ECM, which appears scattered around ICAP-1−/− capillary. Arrowhead points to detachment of the EC from its BL. EC–EC junctions are present (arrow). Bar, 1 µm. n = 4 for each genotype from three litters. (D) Gallery of ear pictures over time under a fluorescence microscope after injection of Alexa Fluor 546/10-kD dextran in the blood circulation. See the progressive increase in fluorescence of the ear tissue in ICAP-1−/− mouse compared with wild-type littermate (yellow rectangle). Bar, 100 µm. (E) Diffusion rate of the 10-kD dextran was calculated between 90 and 300 s after injection. Error bars are means ± SEM (n = 5 for each genotype from five litters for +/+ and two litters for −/−). *, P < 0.05 one-tailed paired t test.