The use of the vaccinia virus complement control protein (VCP) in the rat retina

Abstract

The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown to be effective as a complement inhibitor in neuroinflammatory models including traumatic brain injury and spinal cord injury. We aimed to investigate the potential of VCP as a therapeutic molecule for retinal degenerations. In this study, we investigated the effect, localisation and delivery of VCP to the rodent retina. Complement inhibition activity of VCP was tested using a hemolytic assay. Photoreceptor cell death, inflammation and retinal stress were assayed to determine if any retinal toxicity was induced by an intravitreal injection of VCP. The effect of VCP was investigated in a model of photo-oxidative retinal degeneration. Localisation of VCP after injection was determined using a fluorescein-tagged form of VCP, as well as immunohistochemistry. Finally, a copolymer resin (Elvax) was trialled for the slow-release delivery of VCP to the retina. We found that a dose equivalent to 20|jg VCP when intravitreally injected into the rat eye did not cause any photoreceptor cell death or immune cell recruitment, but led to an increase in GFAP. In photo-oxidative damaged retinas, there were no differences in photoreceptor loss, retinal stress (Gfap) and inflammation (Ccl2 and C3) between VCP and saline-injected groups; however, Jun expression was reduced in VCP-treated retinas. After VCP was injected into the eye, it was taken up in all layers of the retina but was cleared within 1-3 hours of delivery. This study indicates that a method to sustain the delivery of VCP to the retina is necessary to further investigate the effect of VCP as a complement inhibitor for retinal degenerations