Polysialinsäure zur Immunmodulation im Tiermodell der feuchten altersabhängigen Makuladegeneration (AMD)

Abstract

Chronic activation of the innate immune system is a hallmark of retinal degenerative diseases, including age-related macular degeneration (AMD). Overt microglia and macrophage reactivity, as well as dysregulation of the alternative complement system, trigger and sustain retinal degeneration. It is now accepted that there exists a vicious cycle of mononuclear phagocyte reactivity, abnormal intrinsic complement activation, damage of Bruch's membrane, dysfunction of the retinal pigment epithelium, photoreceptor degeneration and choroidal neovascularization (CNV). Targeting the innate immune system may, therefore, be a complementary approach to anti-angiogenic therapy. This article presents data from polysialic acid treatment experiments in the laser-induced mouse model of wet AMD. The laser-CNV mouse model was used to simulate events of neovascular AMD. Polysialic acid was applied by intravitreal injection and microglia activity was assessed with Iba1 staining of retinal and RPE/choroidal flat mounts. Neovascular leakage was determined by fluorescein angiography. Intravitreal injection of polysialic acid reduced retinal and RPE/choroidal lesion-associated microglia activity in the laser-induced mouse model of AMD. Polysialic acid treatment also diminished vascular leakage at laser spots in this model. Local retinal immunomodulation with polysialic acid presents a novel concept for treatment of inflammatory conditions related to neovascular AMD.

Comprehensive Ocular and Systemic Safety Evaluation of Polysialic Acid-Decorated Immune Modulating Therapeutic Nanoparticles (PolySia-NPs) to Support Entry into First-in-Human Clinical Trials

“…PolySia was found to be neuroprotective to the retinal ganglion after kainic acid-induced excitotoxicity [ 33 ]. Intravitreal administration of PolySia was demonstrated to inhibit macrophage recruitment, complement activity, and neovascularization in a laser-induced model of choroidal neovascularization [ 34 , 35 ]. No toxicity study of intravitreal PolySia has been performed, but the endogenous presence of PolySia in the retina and CNS and its therapeutic effect in animal models support the results of this paper, which show no ocular toxicity towards a PolySia-NP.…”