THE EFFECT OF PRINOMASTAT (AG3340), A POTENT INHIBITOR OF MATRIX METALLOPROTEINASE, ON A NEW ANIMAL MODEL OF EPIRETINAL MEMBRANE MOHAMED H. EL-BRADEY, MD,* LINGYUN CHENG, MD,* DIRK UWE BARTSCH, PHD,* MICHAEL NIESSMAN, PHD,† ABBAS EL-MUSHARAF, MD,* WILLIAM R. FREEMAN, MD* Purpose: To develop a simple epiretinal membrane (ERM) animal model and evaluate the efficacy of prinomastat (AG3340), a synthetic inhibitor of matrix metalloproteinase. Methods: This experiment was carried out on 18 eyes of nine Brown Norway rats. Preretinal hemorrhage was induced bilaterally using diode laser focused deeply on cho- roidal blood vessels. One day later, AG3340 was injected intravitreally in the right eyes while the left eyes received equal amounts of vehicle. The developed epiretinal membrane was measured in disk areas and compared between groups. Results: Clinically, preretinal hemorrhage showed a slow clearance persisting for 8 to 10 weeks. ERM was well established around 12 weeks. Histologically, ERMs consist of fibroblast and glial cells embedded in collagen-rich extracellular matrix infiltrated by macrophages. Seventy-five percent of the hemorrhagic laser burns in the control group developed ERM, whereas only 25% of the hemorrhagic laser burns in treated group developed ERM (P = 0.01). The total surface area of developed ERM was 3.66 DD in treated eyes versus 25.45 DD in control eyes (P = 0.049). The mean surface area of ERM per eye was 0.52 disk areas  1.05 in treated eyes versus 3.18  3.07 in control eyes. Conclusion: We demonstrated that ERM can be induced on rat retina by simple hemorrhagic retinal laser coagulation. This new animal model could be used for future evaluation of different medical treatment modalities for proliferating ERM. Furthermore, AG3340 demonstrated an inhibitory effect on ERM formation in this new rat model. RETINA 24:783–789, 2004 E piretinal membrane (ERM) is a cellular prolifer- ation on the retinal surface. This proliferation can occur in cases of several clinical conditions, including ocular trauma, rhegmatogenous retinal detachment, and ocular inflammation. 1–3 ERM can also appear as an idiopathic process in otherwise normal eyes. 4 Few animal models of ERMs have been reported. Matsumoto et al 5 induced ERM in monkeys by per- forming a posterior penetrating injury followed by intravitreal injection of blood and lens material. Kono et al 6 introduced another model of ERM by injecting blood into the vitreous of rabbits without any trauma to the underlying retina. They studied the events in the vitreoretinal interface from 1 week to 1 year of fol- low-up using light and electron microscopy. One week after blood injection, localized protrusion of From the *Jacobs Retina Center, Department of Ophthalmology, University of California, Shiley Eye Center, San Diego, California; and †Agouron Pharmaceuticals, La Jolla, California. Supported by NIH Grant EYO 7366 and Research to Prevent Blindness, Inc., and Agouron Pharmaceuticals (WRF). The authors have no proprietary interest in any products men- tioned in this study. Dr. Niessman is employed by Agouron Pharmaceuticals. Reprint requests: William R. Freeman, MD, Director, Jacobs Retina Center, Shiley Eye Center, University of California San Diego, 9415 Campus Point Drive, La Jolla, CA 92093-0946; e-mail: freeman@eyecenter.ucsd.edu 783