A Mouse Model of Proliferative Vitreoretinopathy Induced by Dispase (original) (raw)

A proliferative vitreoretinopathy-like condition induced by intravitreal dispase injection in C57BL/6J mice was studied using ophthalmoscopic and histochemical procedures. The frequency of intravitreal hemorrhage, intravitreal spots, retinal folds and epiretinal membranes was scored by ophthalmoscopic examination at 1, 2, 4, 6 and 8 weeks after the injection. Intravitreal spots corresponded to free cells exhibiting F4/80 immunoreactivity, a macrophage/microglial marker. Retinal folds always appeared before an epiretinal membrane could be observed. Dispase-injected eyes always showed a much higher frequency of folds and membranes than saline-injected eyes. Folds and membranes appeared earlier and were more extensive in the presence of intravitreal hemorrhage than in its absence. Mu È ller retinal cells exhibited signi®cant changes in glial ®brillary acidic protein-immunoreactivity. This was absent in normal Mu È ller cells but, in dispase-injected animals, it was expressed in radial processes at the site of retinal folds, later extending to the whole retina. Both epi-and subretinal membranes contained cells probably derived from Mu È ller cells, since they exhibited co-localization of glial ®brillary acidic protein-and glutamine synthase immunoreactivities. F4/80 was also present in numerous cells within the retina, epi-and subretinal membranes. By contrast, the retinal pigment epithelium cell marker RPE65 was restricted to subretinal membranes. It can be concluded that dispase induced a proliferative vitreoretinopathy-like condition in mice, with a strong contribution of macrophage-and glial-derived cells.