Ocular neovascularization: potential for the angiopoietin/Tie-2 pathway

The concept of angiogenesis and the intricate molecular pathways involved have provided a better understanding of disease mechanisms in several fields of medicine, including ophthalmology. The combination of ocular neovascularization and/or the associated vascular leakage from VEGF production play an integral role in inducing the significant visual morbidity associated with diabetic retinopathy and age-related macular degeneration. However, although intravitreal anti-VEGF therapy is becoming well established, it is by no means the only angiogenic pathway involved in the pathogenesis of neovascular ocular disease, and it is the aim of this review to summarize the significance of the angiopoietin/Tie pathway (Ang/Tie pathway) in such ocular pathologies. Indeed, it is becoming evident that the Ang/Tie pathway is intricately integrated into the angiogenic cascade, and that the balance in levels of angiopoietin subtypes, Ang:VEGF ratio as well as the localization of Tie-2 in the cellular microenvironment can govern the nature of new vessel formation. However, this review critically analyzes the highly complex and contradictory nature of the Ang/Tie pathway to highlight the difficulties for Ang-2 inhibitors to find their way into the clinical setting to complement the existing anti-VEGF-based therapies.