title: Pro-inflammatory cytokines and gelatinases in climatic droplet keratopathy.
abstract: OBJECTIVE
  Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea with possible involvement from matrix metalloproteinases (MMPs). Therefore, the authors investigated histologic distribution, levels, and molecular forms of MMP-2 and MMP-9, as well as tear fluid levels of MMPs and cytokines in CDK patients. They additionally examined UV-B-irradiation effect on production of gelatinases and cytokines by human corneal epithelial (HCE) cell culture model.
  
  
  METHODS
  Tears were collected from 20 unrelated individuals (10 with CDK and 10 controls). CDK affected corneas were haematoxylin-eosin stained and the presence and distribution of MMP-2 and MMP-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 MMP-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, UV-B increased gelatinase secretion, with a striking effect on MMP-9, and was preceded by pro-inflammatory cytokine release.
  
  
  CONCLUSIONS
  The authors demonstrate that the corneal epithelium could participate in CDK development as a source of cytokines and gelatinases. Additionally, in HCE cells, UV-B- modulated cytokine and subsequent MMP secretion. Local inhibition of cytokine secretion and gelatinases may prevent CDK progression.
authors.affiliation: Helsinki Eye Lab, Department of Ophthalmology, University of Helsinki, Finland. juha.holopainen@hus.fi
authors.forename: Juha M
authors.initials: JM
authors.lastname: Holopainen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Robciuc
authors.forename: Thamara A
authors.initials: TA
authors.lastname: Cafaro
authors.forename: Maria F
authors.initials: MF
authors.lastname: Suarez
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: Hind M
authors.initials: HM
authors.lastname: Alkatan
authors.forename: Khalid F
authors.initials: KF
authors.lastname: Tabbara
authors.forename: Taina
authors.initials: T
authors.lastname: Tervahartiala
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Julio A
authors.initials: JA
authors.lastname: Urrets-Zavalia
authors.forename: Horacio M
authors.initials: HM
authors.lastname: Serra
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002478:Cells, Cultured; D003316:Corneal Diseases / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D018093:Gelatinases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008875:Middle Aged; D013666:Tears / Q000737:chemistry*
chemical_list: D016207:Cytokines; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9