Tag: MLN8054

Purpose Chronic inflammation is a critical process in pterygium development and

Purpose Chronic inflammation is a critical process in pterygium development and progression including promotion of angiogenesis. In the same patients conjunctiva were obtained from the autograft during surgery. Tissue specimens were formalin-fixed and paraffin-embedded. Tissue sections were analyzed with immunohistochemistry with anti-RAGE antibody. Expression and localization of RAGE were evaluated in pterygium and corresponding conjunctiva. Results RAGE expression was detected in the vascular endothelium in all pterygium tissue specimens and most conjunctival specimens. Other cell types exhibited expression notably epithelial cells fibroblasts and possibly macrophages. Strikingly endothelial RAGE expression was increased in 19 MLN8054 of 25 pterygium tissue specimens compared to the corresponding control conjunctiva. Conclusions Our data reveal that RAGE expression is upregulated in vascular endothelial cells in pterygium. RAGE upregulation is an important mechanism by which endothelial cells amplify the overall inflammatory response MLN8054 and suppression of RAGE has been shown to prevent the progression of some systemic disease processes PMCH in experimental models. This suggests that pharmacologic targeting of RAGE which is already being attempted in clinical trials for some diseases could be useful in treating pterygium. Introduction Pterygium MLN8054 is an ocular surface disease related to chronic ultraviolet light exposure. Pterygium is a proliferative invasive process characterized by a fibrovascular conjunctival outgrowth that impinges on the corneal surface. Surgical excision can be a useful therapy for pterygia but recurrences are common. There is a significant need to gain more insight into pterygium formation and recurrence to enable the design of new therapeutic strategies either for inhibiting pterygium growth regressing pterygia or preventing recurrent pterygia. The identification of new molecular pathogenic determinants of pterygia could lead to new therapeutic targets. Chronic inflammation is a critical process involved in the development and MLN8054 progression of pterygium including promotion of angiogenesis [1-3]. Inflammation has classically been conceptualized in leukocytes but vascular endothelial cells (ECs) are now appreciated as active participants and regulators [4]. Pterygium research has uncovered multiple proinflammatory genes that are activated in pterygium tissue including the proinflammatory transcription factor nuclear factor-kappa beta (NF-κB) [5] and several cytokines including tumor necrosis factor α (TNF-α) [6]. However there has been minimal focus on EC activation in pterygium and more insights are needed into additional molecules that could lead to new strategies for pharmacologic treatment. The Receptor for Advanced Glycation Endproducts (RAGE) is a member of the superfamily of immunoglobulin cell-surface receptors that plays an important role in promoting inflammation [7 8 RAGE has multiple ligands including advanced glycation endproducts (AGEs) HMGB1 and S100b. Interaction between RAGE and its ligands prospects to induction of NF-κB and proinflammatory gene activation. RAGE takes on a particularly important part in vascular endothelial cells (ECs) and their activation [9]. Given the importance of endothelial cell activation (for swelling and angiogenesis) in pterygium we are interested in identifying molecular players that might regulate ECs in pterygia. With this study we hypothesized that RAGE a major instigator of endothelial activation is definitely upregulated in ECs in pterygium. We consequently investigated the localization of RAGE in pterygium cells to determine whether RAGE is indicated in vascular endothelial cells. In addition we compared endothelial RAGE manifestation in pterygium cells with manifestation in normal conjunctiva to determine if there is induction of endothelial RAGE in pterygium. Methods MLN8054 Individuals and specimens Pterygium specimens were from 25 individuals during pterygium surgery at the King Khaled Eye Professional Hospital (KKESH). Individuals were in good health and ranged from 17 to 85 years of age with 18 males and 7 females (Table 1). Pterygium specimens were acquired during pterygium surgery at the King Khaled Eye Professional Hospital (KKESH). All individuals underwent pterygium excision rotational conjunctival flap software of (mitomycin C) MMC 0.2?mg/ml × 1 min. Two individuals required amniotic membrane transplantation (AMT) to protect bare sclera. In the same individuals 1.5 × 1.5?mm conjunctiva specimens were acquired.