Yingli Fu, Bioengineering, University of Maryland, College Park, 10 Center Drive, Building 10, Rm10B11, Bethesda, MD 20892, Nam Sun Wang, Chemical and Biomolecular Engineering, University of Maryland, College Park, MD 20742, and Karl G. Csaky, National Eye Institute, National Institutes of Health, 10 Center Drive, Bldg 10 / 10B11, Bethesda, MD 20892.
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. Furthermore, the low therapeutic index of the majority of the drugs used for posterior segment diseases may require a drug concentration injected intravitreally at or near the toxic level to the retina. 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.
Both types of EMD microimplants inhibited CNV relative to controls in a statistically significant fashion. 7 days after laser, in the eyes that received implant A the mean CNV area of the recovered lesions measured 24920 mm^2, while those received microimplant B were 23656 mm^2, compared to 59850 mm^2 for the recovered lesions from the fellow control eyes. 14 days after laser, in the eyes that received implant A, the mean CNV area of the recovered lesions measured 41295mm^2, while those received microimplant B were 39522 mm^2, compared to 112794 mm^2 for the recovered lesions from the fellow control eyes. This study provides evidence that EMD may be useful in the treatment of eye diseases associated neovascularization via long acting sustained release intraocular microimplants.