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Purpose: Both the cellular and non-cellular components of the innate immune system are strongly implicated in the pathophysiology of age-related macular degeneration (AMD). Inhibition of the complement system has been shown to decrease the rate of progression of geographic atrophy in randomized clinical trials. We report a novel therapeutic strategy to address chronic inflammation in the retina by modifying the body’s own self-recognition system on immune cells. The therapeutic molecule AVD-104 (Aviceda Therapeutics, Cambridge, MA) is an engineered dual function glycan (sialic-acid) nanoparticle that directly modulates the self-pattern recognition receptors on immune cells called Siglecs (sialic-acid binding immunoglobulin-like lectins), thereby dampening the inflammatory activity of macrophages and microglia. The significant anti-inflammatory effect of AVD-104 has been previously confirmed in in-vitro experiments. Additionally, AVD-104 has been shown to enhance the activity of complement factor H and down-regulate the alternative complement cascade and has been shown to be safe in 3 species, including non-human primates.

Methods: AVD-104 was intravitreally (IVT) injected in humanized Siglec transgenic mice to assess efficacy in both the bright light damage (BLD) model of retinal degeneration (n= 15 eyes) and the laser-induced model of choroidal neovascularization (CNV, n= 21 eyes). In the BLD model, animals were given an IVT injection of AVD-104 one day before intense light exposure and examined 7 days later. In the laser CNV model, animals were given an IVT injection of AVD-104, lasered on the same day, and …