A Mouse Model of Proliferative Vitreoretinopathy Induced by Dispase

Abstract

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. Müller retinal cells exhibited significant changes in glial fibrillary acidic protein-immunoreactivity. This was absent in normal Müller 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 Müller cells, since they exhibited co-localization of glial fibrillary 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.