The effect of prinomastat (AG3340), a potent inhibitor of matrix metalloproteinase, on a new animal model of epiretinal membrane.
OBJECTIVE
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 choroidal 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.


CONCLUSIONS
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.
El-Bradey
Mohamed H
MH
Jacobs Retina Center, Department of Ophthalmology, University of California, Shiley Eye Center, San Diego, California, USA.
Cheng
Lingyun
L
Bartsch
Dirk Uwe
DU
Niessman
Michael
M
El-Musharaf
Abbas
A
Freeman
William R
WR
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D019773:Epiretinal Membrane / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005260:Female; D007267:Injections; D017075:Laser Coagulation / Q000009:adverse effects; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D012166:Retinal Hemorrhage / Q000209:etiology / Q000473:pathology; D014822:Vitreous Body
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; C113282:prinomastat