Project: X04

CD83-related immunomodulation of retinal microglia in age-related macular degeneration

This crosslinking project investigates the immunomodulatory potential of soluble CD83 (sCD83) in retinal inflammation and neovascular retinal disease. sCD83 is a powerful anti-inflammatory and pro-resolving mediator known to induce immune tolerance, promote wound healing, stimulate tissue regeneration, and inhibit inflammatory cell death. Previous collaborative work within SFB 1607 demonstrated that topical application of recombinant sCD83 significantly improves corneal graft survival, while additional studies identified CD83 as an important regulator of microglial activation in neuroinflammatory diseases of the brain. Building on these findings, this project aims to explore whether the CD83/sCD83 signaling axis also controls retinal microglia and inflammatory responses in retinal degeneration.

The project combines expertise from projects B03, C05, and C06, with additional conceptual links to A02 and A03, thereby connecting mechanisms of ocular surface immunity with immune regulation in the posterior segment of the eye. The central objective is to evaluate the therapeutic potential of sCD83 in neovascular age-related macular degeneration (AMD) using the laser-induced choroidal neovascularization (laser-CNV) mouse model. Systemic treatment with recombinant sCD83 will be assessed using in vivo retinal imaging approaches and detailed molecular and cellular analyses of retinal inflammation and angiogenesis.

In parallel, tamoxifen-inducible, microglia-specific CD83 knockout mouse models will be used to investigate the role of endogenous CD83 signaling in retinal immune homeostasis, microglial activation, gliosis, and myeloid cell infiltration. Complementary transcriptomic analyses will further characterize immune regulatory pathways associated with CD83 signaling and establish a reference dataset for future sCD83-related projects within SFB 1607.

By extending the concept of sCD83-mediated immunomodulation from the ocular surface to the retina, this project establishes a new interdisciplinary framework for understanding immune regulation in retinal disease. The findings may identify sCD83 as a novel therapeutic strategy for retinal inflammatory and neovascular disorders while further strengthening the SFB 1607 focus on cellular immunomodulation and control of pathological (lymph-)angiogenesis.

Key Methods