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Michael Raghunath, Rasim Cankay, Ulrich Kubitscheck, Jan Dirk Fauteck, Richard Mayne, Daniel Aeschlimann, Ursula Schlötzer–Schrehardt; Transglutaminase Activity in the Eye: Cross-linking in Epithelia and Connective Tissue Structures. Invest. Ophthalmol. Vis. Sci. 1999;40(12):2780-2787.
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purpose. To assess the distribution of transglutaminase (TGase) activity in
ocular tissues and the target structures for cross-linking.
methods. Cryosections from human and cynomolgus monkey eyes were incubated with
the biotinylated amine donor substrate cadaverine (biotC), which was
subsequently visualized with streptavidin-peroxidase. Confocal laser
scanning was used to colocalize biotC and fibrillin, a major component
of elastic microfibrils and the zonular fibers in particular.
Cryosections and isolated bovine zonules were treated with purified
TGase 2 and biotC. The distribution of different TGases (1, 2, 3, and
factor XIII) was confirmed immunohistochemically.
results. Virtually all ocular tissues showed TGase activity with a remarkable
preponderance for the ciliary body, zonular fibers, and blood vessel
walls. Confocal laser scanning revealed fibrillin-containing
microfibrils as a major target for TGase activity, in particular the
ciliary zonules. Corneal epithelium and basement membrane showed a
TGase cross-linking pattern similar to skin. Treatment of cryosections
and isolated bovine zonular fibers with purified TGase 2 led to
additional incorporation of biotC into extracellular matrix,
particularly zonular fibers. The immunohistochemically predominant
TGase 2 was associated with epithelia and particularly with connective
tissue fibers. TGase 1 was restricted to the corneal epithelium,
whereas factor XIII was found to be associated only with blood vessels.
TGase 3 was absent.
conclusions. TGase 2 appears to be an important cross-linker and thus stabilizer of
ocular connective tissue. In particular, the zonular fibers are a major
target for TGase 2. This is of relevance in hereditary
microfibrillopathies such as Marfan syndrome, which exhibits distinct
ocular manifestations such as elongated bulbus, retinal detachment, and
subluxation of the lens. Purified or recombinant TGase might be of
therapeutic use in the future.
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