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R. Greemberg, N. Gasemlou, F. Zakka, S. David, C. S. Foster; Secretory Leukocyte Protease Inhibitor in Conjunctivae Affected by Ocular Cicatricial Pemphigoid. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5524.
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Conjunctivae blisters and mucosal scarring is an important histological feature of ocular cicatricial pemphigoid (OCP), a complex autoimmune disease characterized by immunoglobulin deposits on the epithelial basement membrane zone (BMZ) and the presence of inflammatory mediators such as tumor necrosis factor- (TNF-). Secretory leukocyte protease inhibitor (SLPI), a gene product of epithelial cells lining mucosal tissues and inflammatory immune cells, has been known to have anti-bacterial and anti-inflammatory properties in addition to a non-redundant role in cutaneous wound healing. SLPI is known to reduce TNF- expression, as well as regulate immunoglobulin class switching. We studied the presence of SLPI in conjunctivae affected by OCP.
Biopsy specimens from conjunctiva of 6 patients with OCP, 6 normal subjects undergoing cataract surgery and 2 patients with atopic keratoconjunctivitis (AKC) were assessed by immunohistochemistry for the expression of SLPI. Specimens were co-labeled with an antibody against collagen IV, which served as a marker for the epithelial BMZ and conjunctivae vasculature.
SLPI immuno-positive epithelial BMZ was detected in conjunctivae of normal and OCP subjects, but not in patients with AKC. Normal and AKC specimens showed no evidence of basement membrane separation or sub-epithelial blister formation. OCP epithelium, however, exhibited immunoreactivity for SLPI in proximity to the sub-epithelial blisters. Normal and AKC specimens exhibited vascular endothelia that were consistently immuno-negative for SLPI. In contrast, OCP stroma contained several instances of vasculature which was immuno-postive for SLPI.
: Both OCP and normal epithelial BMZ show SLPI expression in the conjunctivae. In sharp contrast to normal and AKC conjunctiva, SLPI expression in OCP is specific around subepithelial blisters and within the stroma vasculature. Together, these findings suggest a possible new role for SLPI in the pathogenesis of epithelial separation and blister formation and highlight the potential role of vasculature in OCP. Whether SLPI expression in the conjunctivae is indicative of an inflammatory response resolution or an innate protective effect remains to be determined.
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