(609b) Sustained Delivery of an Integrin Antagonist Inhibits Laser Induced Choroidal Neovascularization in Rat Model
AIChE Annual Meeting
2006 Annual Meeting
Discovery, Development and Delivery of Medicines
Protein Product Drug Formulation and Delivery
Thursday, November 16, 2006 - 3:35pm to 3:55pm
Ocular angiogenesis or the formation of new blood vessels in the eye is the leading cause of blindness in a variety of clinical conditions. However, the current treatments available for retina or choroidal neovascularization, including conventional laser therapy and photodynamic therapy, are not optimal, and have their limitations due to frequent treatment, significant recurrence and central visual loss. Although the pathogenesis of this angiogenesis process is still uncertain, several key steps of the angiogenic cascade have been cleared. Previous studies have shown that angiogenesis is partially regulated by integrins; therefore, selective integrin antagonists may lead to a novel integrin-based therapeutic development for the treatment of ocular neovascularization. However, traditional drug delivery methods (i.e. topical, systemic, and periocular) are difficult to delivery therapeutic level of drugs into the posterior segment of the eye and intravitreal injections frequently require repeated ocular drug application. Consequently, new strategies need to be explored to solve these problems. Sustained drug delivery devices offer an excellent alternative to multiple intravitreous injections. In this study, we developed a micro-implant, releasing an integrin antagonist, EMD, and studied the anti-angiogenic effect of this integrin antagonist in a laser-induced choroidal neovascularization (CNV) rat model. 15 Norway brown rats were anesthetized. Four laser lesions were concentrically created around the optic nerve. Formation of a bubble indicated rupture of Bruch's membrane. In the current study, an EMD microimplant was placed within the vitreous chamber of the right eye and the left eye received a control implant. The rats were sacrificed 1 week or 2 weeks after laser and perfused immediately with FITC-Dextran. CNV area was measured from the flat mount of the recovered eyes. EMD microimplants inhibited CNV relative to controls in a statistically significant fashion. 7 days after laser, in the eyes that received EMD microimplant, the mean CNV area of the recovered lesions decreased 39% compared with the recovered lesions from the fellow control eyes. 14 days after laser, the CNV area from microimplant treated group reduced 60% compared with control. This study provides evidence that EMD may be useful in the treatment of eye diseases associated neovascularization via long acting sustained release intraocular microimplants.