Are proteinases the reason for keratoconus?
OBJECTIVE
Keratoconus is a degenerating disease of the eye that results in an irregularly-shaped cornea. The etiology of the disease is unknown and the prognosis is difficult due to the variability in outcome. Keratoconus has been associated with eye rubbing, atopy, contact lens wear, as well as genetic conditions, such as Down's syndrome, Ehlers-Danlos syndrome, and Marfan's syndrome. Thinning of the cornea in keratoconus has been well studied and is documented to occur as a result of degradation of corneal collagen. The reason for this tissue degradation is unknown but has been hypothesized to be linked with proteases.


METHODS
This study used a literature search to review the role of proteases and inflammatory molecules in the aetiology of keratoconus.


RESULTS
Early studies demonstrated elevated levels of collagenolytic and gelatinolytic activities in laboratory cultures of keratoconic corneas. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteins that include collagenases and gelatinases. MMPs levels are altered in keratoconus corneas compared to normal corneas and the level of tissue inhibitor of metalloproteinases-1 (TIMP-1) is decreased in keratoconic corneas. Recent studies have demonstrated the involvement of Cathepsin B, G, and K in keratoconus. Although thought to be a non-inflammatory disease, inflammatory molecules, such as interleukins and tumor necrosis factor have been shown to be elevated in keratoconus, and these inflammatory molecules may mediate production and activation of proteases.


CONCLUSIONS
Proteases may be implicated in keratoconus. An in-depth investigation of these proteases may help in better understanding the course of the disease.
Balasubramanian
Sivaraman A
SA
School of Optometry and Vision Science, The University of New South Wales, Sydney, NSW, Australia. sivaramanbala10@gmail.com
Pye
David C
DC
Willcox
Mark D P
MD
D002403:Cathepsins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003319:Corneal Stroma / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000201:enzymology*; D020782:Matrix Metalloproteinases / Q000502:physiology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D002403:Cathepsins; D020782:Matrix Metalloproteinases