The role of lumican in ocular disease

Abstract

Lumican is keratan sulfate proteoglycan of the small leucine rich proteoglycan family. Through studies in animal models lumican has been found to be critical in maintaining corneal clarity. It maintains ordered collagen fibrils which are vital in keeping the cornea transparent. It may also be important in primary open angle glaucoma influencing aqueous outflow. Lumican deficiency in mice results in increased axial length with fibromodulin deficiency and thinner sclerae. There is evidence suggesting that this characteristic may be pertinent in humans and lumican gene polymorphisms could be related to high myopia. Lumican plays a fundamental role in inflammation and wound healing. It localises macrophages to the site of corneal injury and recruits neutrophils in lipopolysaccharide-induced keratitis in mice. It has also been shown to bind lipopolysaccharide which may be critical in inflammatory diseases such as uveitis. Lumican is also important in wound healing revealing decreased synthesis in scar tissue and mediating Fas-Fas ligand interactions. It is present in human placenta and amniotic membrane suggesting that it may ensure viable amniotic membrane grafts. Lumican may also be involved in the formation of posterior capsular opacification following cataract surgery. Research into the pivotal role of lumican in the pathogenesis of ocular disease has resulted in greater understanding of the key role which proteoglycans play in human disease.

Figure 1

(a) Transverse view of corneal stroma with ordered arrangement of collagen fibrils (circles) with proteoglycan attachments anchoring the fibrils and maintaining their spatial order [21]. (b) Where there is a deficiency or defect in lumican, collagen fibrillar structure is not maintained.

Figure 2

(a) When LPS binds to TLR4, with the cobinding molecule CD14, it leads to downstream production of proinflammatory cytokines via the NF-κB transcription factor [53]. (b) Lumican by binding to LPS augments this response leading to increased production of proinflammatory cytokines [41].

Figure 3

Lumican staining in human iris pigment epithelial cells (IPE) and iris. Human IPE cultures (A, D), iris tissues (B, E). Lumican staining (red) is present in IPE in vitro (D) and in vivo (E), in blood vessels (bv) (F).