June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Matrix Metalloproteinase-9 drives disease progression of Keratoconus
Author Affiliations & Notes
  • ashwini ranganath
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Rohit Shetty
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Sharon D'Souza
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Kareeshma Wadia
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Debashish Das
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Arkasubhra Ghosh
    cornea and refractive surgery, Narayana Nethralaya eye hospital, Bangalore, India
  • Footnotes
    Commercial Relationships ashwini ranganath, None; Rohit Shetty, None; Sharon D'Souza, None; Kareeshma Wadia, None; Debashish Das, None; Arkasubhra Ghosh, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4070. doi:
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      ashwini ranganath, Rohit Shetty, Sharon D'Souza, Kareeshma Wadia, Debashish Das, Arkasubhra Ghosh; Matrix Metalloproteinase-9 drives disease progression of Keratoconus. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4070.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

Keratoconus is a corneal thinning disorder of unknown etiology for which no drugs or therapies are available currently. Furthermore, the exact cause of stromal thinning is not clear. Matrix metalloproteinases are upregulated during matrix remodeling and cause degradation of various types of collagen. MMP9 has been demonstrated to degrade typeI and IV collagen fibers in cancer. This activity is regulated by cytokine Interleukin 6(IL6). We therefore asked whether MMP9 is upregulation in keratoconus correlates to increasing stages of disease and depends on abnormal IL6 levels. We quantified levels of MMP9 and IL6 in tear films of keratoconus patients and correlated with severity of disease. To validate our hypothesis we investigated effect of topical CsA(cyclosporine A)treatment in keratoconus as it has been demonstrated to inhibit MMP9 and has been approved for treatment of allergic eye disease.

 
Methods
 

64 eyes with keratoconus of varying severity were included. This study and on label use od CsA to treat associated with keratoconus was approved by Narayana Nethralaya IRB. Keratoconus was graded based on topographic criteria of Keratoconus Severity Index using steep K into <48 D, 48-51 D, 51-56 D and >56D. Tear samples were collected from lower fornix with capillary tubes. Levels of MMP-9 and IL6 in each sample were measured by ELISA and were correlated with severity of keratoconus. 10 patients with progressive keratoconus were treated with topical CsA 0.05% and topography was analyzed pre and post treatment (6 months and 1 year) to evaluate stability of keratoconus.

 
Results
 

Mean MMP9 (Normal 3.9-8.3 ng/ml) and IL6 (normal 1-4.1) respectively were 42.45 and 1.03 in <48 D group, 40.06 and 1.125 in 48-51 D group, 46.07 and 1.64 in 51-56 D group and 46.55 and 1.06 in >56 D group. Of 10 patients treated with CsA, 8 showed stabilization of keratoconus, and 6 had flattening of keratometry ranging from 0.5-1.7D, 6 months to 1 year post treatment.

 
Conclusions
 

Significantly higher levels of MMP9 and marginally higher levels of IL6 were detected in tear samples of keratoconus eyes, and their levels positively correlated with severity of keratoconus. Inhibiting MMP9 locally in cornea using CsA halted disease progression and even reduced the disease in few cases. This suggests MMP9 is an important factor driving keratoconus pathophysiology. Also, topical CsA may be an effective disease modifying agent in keratoconus management.

 
Keywords: 574 keratoconus • 490 cytokines/chemokines • 489 cyclosporine  
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