Gene Transfer of Bioactive IL–1ß to the Anterior Chamber of the Rodent Eye Induces a Retinal Phenotype Similar to Human Proliferative Vitreoretinopathy

Abstract

Abstract: : Purpose: We have made use of our previously validated adenoviral gene transfer method to over–express relevant bioactive cytokines in the mouse eye in an attempt to create a murine model of proliferative vitreoretinopathy (PVR). Methods: Recombination–deficient adenovirus containing the transgene encoding human IL–1ß was injected into the anterior chamber of 6–8 week old C57 black mice. Four days post injection, animals were enucleated and eyes were processed for routine histology. In addition, we used immunohistochemical techniques to localize proliferating cell nuclear antigen (PCNA) for examining cell proliferation, and alpha smooth muscle actin (αSMA) for detecting cells with a myofibroblastic phenotype, characteristic of PVR. Results: In contrast to control–vector treated animals, inflammatory cells were found in all parts of the anterior chamber as well as in the vitreous chamber of IL–1ß–vector treated animals. Although the extent of inflammation was significant, there were no gross anatomical alterations in the structures of the anterior chamber. The outer nuclear layer of the retina, however, showed extensive folding without any obvious increase in cellularity. Extensive expression of PCNA was confined to the nuclei of cells in the inner nuclear layer. αSMA expression was detected in multiple retinal layers of the IL–1ß–vector treated animals including the inner nuclear and outer plexiform layers and the retinal pigmented epithelium. All of these retinal alterations were not observed in control–vector treated animals.<br /Conclusions: Animals treated with IL–1ß exhibited a phenotype similar to human proliferative vitreoretinopathy, including increased retinal proliferation and αSMA expression. IL–1ß is known to be significantly elevated in the vitreous humor of patients with PVR prior to retinal detachment surgery however the levels are not significantly raised in patients with recurrent PVR post–surgery. This suggests that there are other downstream effectors leading to this retinal disease, the identity of which may be pursued using this model.

Keywords: cytokines/chemokines • adenovirus • proliferative vitreoretinopathy