PRO INFLAMMATORY CYTOKINES AND GELATINASES IN CLIMATIC DROPLET KERATOPATHY

M. HOLOPAINEN, J.; ALEXANDRA ROBCIUC; A. CAFARO, THAMARA; MARIA F. SUAREZ; YRJÖ T. KONTTINEN; KHALID F. TABBARA; TAINA TERVAHARTIALA; T. SORSA,; A. URRETS-ZAVALÍA, JULIO; HORACIO M. SERRA

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

ASSOC RESEARCH VISION OPHTHALMOLOGY INC

Lugar: Rockville, MD 20852; Año: 2012 vol. 53 p. 3527 - 3535

0146-0404

Purpose: Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea with possible involvement from matrix metalloproteinases (MMPs). Therefore, we investigated histological distribution, levels and molecular forms of MMP-2 and 9 as well as tear fluid levels of MMPs and cytokines in CDK patients. We additionally examined ultraviolet B (UV-B)-irradiation effect on production of gelatinases and cytokines by human corneal epithelial (HCE) cell culture model. Methods: Tears were collected from twenty unrelated individuals (ten with CDK and 10 controls). CDK affected corneas were haematoxylin-eosin stained and the presence and distribution of MMP-2 and -9 was examined using immunohistochemistry. Gelatinases and cytokine secretion was measured in tears and supernatants from UV-B-exposed HCEs by immunoblotting, gelatin zymography and protein array, respectively. Results: MMP-2 and -9 values were significantly higher in tears collected from CDK patients than healthy controls and were accompanied by pro-inflammatory cytokine secretion. Immunohistochemistry showed that MMP-2 was expressed at the basement membrane zone in both control and affected corneas but also marked the edges of the granular CDK deposits; MMP-9 expression was restrained to basal layers of the epithelium and was markedly induced in CDK corneas. In HCE cells, UVB increased gelatinase secretion, with a striking effect on MMP-9, and was preceded by pro-inflammatory cytokine release. Conclusion: We demonstrate that the corneal epithelium could participate in CDK development as source of cytokines and gelatinases. Additionally, in HCE cells, UV-B modulated cytokine and subsequent MMP secretion. Local inhibition of cytokine secretion and gelatinases could prevent CDK progression.