rss
Br J Ophthalmol 2005;89:169-173 doi:10.1136/bjo.2004.044685
  • Clinical science
    • Extended reports

Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome

  1. S L Ho1,
  2. G F Dogar2,
  3. J Wang3,
  4. J Crean4,
  5. Q D Wu3,
  6. N Oliver5,
  7. S Weitz5,
  8. A Murray2,
  9. P E Cleary2,
  10. C O’Brien1
  1. 1Department of Ophthalmology, Mater Misericordiae Hospital, Conway Institute, Dublin, Ireland
  2. 2Department of Ophthalmology, Cork University Hospital, Cork, Ireland
  3. 3Surgical Research Laboratory, Cork University Hospital, Cork, Ireland
  4. 4Department of Medicine and Therapeutics, Conway Institute, University College Dublin, Ireland
  5. 5FibroGen, Inc, South San Francisco, CA, USA
  1. Correspondence to: Su Ling Ho Department of Ophthalmology, Mater Misericordiae Hospital, Eccles Street, Dublin 7, Ireland; sulinghoeircom.net
  • Accepted 8 July 2004

Abstract

Background/aims: Pseudoexfoliation syndrome (PXF) was recently found to be associated with increased expression of transforming growth factor β1 (TGFβ1) in the aqueous humour. As concern has been raised regarding anti-TGFβ therapy, which can potentially disrupt the maintenance of anterior chamber asso-ciated immune deviation, the authors explored the levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF) in aqueous humour to determine if these may represent alternative therapeutic targets.

Methods: Aqueous humour samples were collected from patients who underwent routine cataract surgery. All patients were categorised into three main groups—PXF, uveitis, and control. The PXF group was further subcategorised into three grades based on the density of the exfoliative material observed on biomicroscopy, as well as the presence or absence of glaucoma. TIMP-1, MMP-9, and CTGF levels were measured using specific enzyme immunoassays (ELISA).

Results: Eyes with PXF had significantly higher aqueous humour TIMP-1 concentration (n = 56, mean (SE), 9.76 (1.10) ng/ml) compared with controls (n = 112, 5.73 (0.43) ng/ml, p<0.01). Similarly, the CTGF level in PXF eyes (n = 36, 4.38 (0.65) ng/ml) was higher than controls (n = 29, 2.35 (0.46) ng/ml, p<0.05). Further, the CTGF concentration in the PXF glaucoma group is significantly higher compared with PXF eyes without glaucoma (6.03 (1.09) ng/ml v 2.73 (0.45) ng/ml, p<0.01). The MMP-9 levels were low and below detection limit in all PXF and control samples with no statistical difference between groups.

Conclusion: A raised TIMP-1 level and a low MMP-9 level in aqueous humour of PXF eyes may imply a downregulation in proteolytic activity. The increased CTGF concentration supports the proposed fibrotic pathology of PXF. Regulation of MMP/TIMP expression and anti-CTGF therapy may offer potential therapeutic avenues for controlling PXF associated ocular morbidity.

Footnotes

  • Supported in part by research grants from Mater College for Postgraduate Education and International Glaucoma Association.

This Article

  1. Abstract
  2. Full text
  3. PDF

Responses

  1. Submit a response
  2. No responses published

Register for free content

The full back archive is now available for all BMJ Journals. Institutional subscribers may access the entire archive as part of their subscription. Personal subscribers will also have access to all content when logged in. Non-subscribers who register have free access to all articles published before 2006 right back to volume 1 issue 1. Register here to access the free archive of all BMJ Journals.

Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.