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E. Jones, K. Mireskandari, A. Mead, S. Thomas, P. Luthert, S. Brocchini, S. Shaunak, P.T. Khaw; The effect of novel immuno–modulatory and anti–angiogenic glycodendrimers in a rabbit model of glaucoma surgery . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1053.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:An in vivo study was undertaken in a well established rabbit model of glaucoma surgery and subconjunctival scarring to assess the effect of two novel synthetic glycodendrimers. A dendrimer is a hyperbranched synthetic polymer that has a multitude of peripheral endgroups that can be utilised for multivalent interactions. In vitro, dendrimer glucosamine (DG) reduced lipopolysaccharide induced release of pro–inflammatory chemokines (MIP–1Î±, MIP–1Î² and IL–8) and pro–inflammatory cytokines (TNFÎ±, IL–1Î²and IL–6) from human macrophages and dendritic cells. Dendrimer glucosamine sulphate (DGS) displayed anti–angiogenic activity in 2 in vitro human model systems. DG and DGS were tested in combination in the rabbit model. Methods:Thirty New Zealand white rabbits underwent experimental glaucoma filtration surgery, as previously described by our group, with a fornix based conjunctival flap and a 22G venflon secured through a scleral tunnel. The rabbits were randomised to subconjunctival (sc) + intraperitoneal(ip) therapy, or to the carrier (sc + ip). The injections were given 2 days pre–operatively, on the operation day, and at intervals of 1–4 days post–operatively. The animals were observed post–operatively by a masked reader for 30 days. Bleb survival was the primary efficacy endpoint with failure defined as the appearance of a flat, scarred bleb with a deep anterior chamber. Results: The combination of DG and DGS significantly improved the success rate of the surgery 80% versus 30% survival (p=0.029) at day 30. No corneal, conjunctival or systemic toxicity was seen. Conclusions: Current treatments for the inflammatory response associated with glaucoma surgery are limited to steroids and immunosuppressants. Severe side–effects include cataract formation and infection. This combination of two novel dendrimer glycoconjugates offers new therapeutic opportunities for controlling excessive scar formation after eye surgery.
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