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Neutrophil accumulation correlates with type IV collagenase/gelatinase activity in endotoxin induced uveitis

Inflammation Research Unit, Department of Pathology, University of New South Wales, Sydney, NSW, Australia

Correspondence to:
Correspondence to:
Nick Di Girolamo, PhD, Inflammation Research Unit, Department of Pathology, The University of New South Wales, Sydney, 2052, Australia;
n.digirolamo{at}unsw.edu.au

ABSTRACT
Background/aim: Anterior uveitis is a common inflammatory ocular disease characterised by protein accumulation and leucocyte infiltration in the anterior chamber. The aim of this study was to determine the expression of gelatinases in the aqueous humour (AH) and uvea in an animal model of endotoxin induced uveitis (EIU).

Methods: EIU was established in Lewis rats following an intraperitoneal injection of lipopolysaccharide (LPS). AH and ocular tissue were obtained from control animals and those with EIU over a 1 week time course and the samples analysed immunohistochemically and by gelatin zymography.

Results: Matrix metalloproteinase (MMP) 2 and 9 levels were elevated in rat AH over a 1 week time course. MMP-2 and MMP-9 levels peaked at the time of maximum uveal inflammation, before returning to baseline levels as the inflammation subsided. MMP-9 was detected in the latent and functionally active form. Total protein extracted from inflamed rat uveal tissue displayed no significant gelatinolytic modulation throughout the time course of EIU. Anterior chamber neutrophils and ciliary body epithelial cells were the most abundant source of the gelatinases.

Conclusion: This study has revealed a correlation between infiltrating neutrophils and the presence of elevated gelatinases in EIU. The results suggest that these proteolytically active enzymes may be important mediators of the inflammatory response and contribute to matrix remodelling observed in uveitis. Furthermore, the excess production of MMPs may be a mechanism by which leucocytes, such as neutrophils, gain access to uveal tissue and AH. Therapeutic strategies aimed at reducing MMP activity may be of some benefit in the treatment of uveitis.

Keywords: aqueous humour; inflammation; lipopolysaccharide; metalloproteinases

Abbreviations: AH, aqueous humour; EAU, experimental autoimmune uveoretinitis; EIU, endotoxin induced uveitis; LPS, lipopolysaccharide; MMP, matrix metalloproteinase; MT-MMPs, membrane associated MMPs; PBS, phosphate buffered saline; TIMPs, tissue inhibitors of MMPs

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