Endothelial Tip Cells in Ocular Angiogenesis: Potential Target for Anti-Angiogenesis Therapy

Ocular diseases dominated by neovascularization, such as age-related macular degeneration (AMD), retinal vein occlusions, and diabetic retinopathy (DR), often culminate in severe visual loss and ultimately blindness. In most of these conditions, ischemic retinal areas produce abnormal amounts of angiogenic growth factors that induce excessive angiogenesis, overwhelming the effects of natural angio-genesis inhibitors (Witmer et al. 2003). The newly formed vessels occur as part of wound-healing responses and usu-ally do not restore tissue integrity. Vision is disturbed when bleeding occurs by secondary macular edema, or when ves-sels finally grow into normally avascular transparent tissues such as the fovea and vitreous and develop into scar tissue (Schlingemann 2004). The most widely used therapeutic target in treating ocular neovascularization is vascular endothelial growth factor-A (VEGF-A) (Witmer et al. 2003). Currently, VEGF-A antagonists are standard care in the treatment of exudative AMD and have been found to be a valuable additional treatment strategy in several other vascular retinal diseases (Schlingemann and Witmer 2009). VEGF and other endogenous factors that can drive angiogenesis have been studied in detail in the past decades, 467635 JHCXXX10.1369/0022155412467635Sie merink et al.Tip Cells in Ocular Angiogenesi