In quiescent retinal vessels, adjacent endothelial cells (ECs) form a tightly sealed junction, leading to maintenance of vascular integrity. By contrast, during pathological angiogenesis in diabetic retinopathy and age-related macular degeneration, vascular endothelial growth factor (VEGF) activates intracellular signaling pathways in ECs, resulting in the dissociation of cell-cell adhesions and induction of EC migration. To inhibit undesirable angiogenesis, it would be clinically beneficial to manipulate intracellular signals that control migratory behavior of ECs. Here we show that the small GTPase RhoJ is expressed predominantly in angiogenic ECs, and regulates cell motility through cytoskeletal rearrangement. We also found that Arhgef15, an EC-specific guanine nucleotide exchange factor, inactivates RhoJ downstream of VEGF signals, thereby promoting retinal vascular growth. These signaling molecules can be potential drug targets for novel anti-angiogenic therapy.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 117: 903-910, 2013.