The Potential of Lenalidomide to Control Scarring in Experimental Models of Glaucoma Filtration Surgery

Abstract

Purpose: : Angiogenesis and inflammation play key roles during wound healing. Both anti-inflammatory and anti-angiogenic medicines showed anti-scarring properties following Glaucoma Filtration Surgery (GFS). Immunomodulating agents such as thalidomide also possess both anti-angiogenic and anti-fibrotic effects. Our aims were (i) to investigate the potential of the thalidomide analogue, lenalidomide, to modulate experimental models of fibrosis and (ii) to determine if lenalidomide could be fabricated into a prolonged dosage form for use in GFS.

Methods: : A collagen gel contraction assay with human tenon fibroblasts (HTF) and a lipopolysaccharide (LPS) induced inflammatory co-culture (RPE and microglia) gel contraction assay were used to determine the in vitro effects of lenalidomide (20 µg/mL). A delayed release lenalidomide tissue tablet was then fabricated and the release profile determined using a flow rig. The tablet was sterilised with gamma irradiation and examined for degradation by HPLC. A preliminary in vivo study using a well characterised rabbit scarring model for GFS was conducted to determine the effect of lenalidomide to modulate on the scarring and its local toxicity.

Results: : Lenalidomide had no significant effect on the fibroblast collagen contraction gel. However, it significantly (p<0.05) inhibited gel contraction in the inflammatory co-culture model. The tissue tablet release profile showed a near first order kinetic for almost a week with approximately 75% of the drug being released. A preliminary in vivo study showed the tablet had disappeared by day 22.

Conclusions: : Immunomodulating medicines including lenalidomide may be beneficial in the control of scarring following GFS. A tissue-tablet was fabricated to determine the potential to deliver a slow and prolonged release of lenalidomide after GFS.

Keywords: wound healing • inflammation • drug toxicity/drug effects