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John M. B. Bradley, Ann Marie Anderssohn, Christine M. Colvis, Dorothy E. Parshley, XiangHong Zhu, Michael S. Ruddat, John R. Samples, Ted S. Acott; Mediation of Laser Trabeculoplasty–Induced Matrix Metalloproteinase Expression by IL-1β and TNFα. Invest. Ophthalmol. Vis. Sci. 2000;41(2):422-430.
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purpose. Laser trabeculoplasty of the anterior uveal region of the trabecular
meshwork induces sustained matrix metalloproteinase expression within
the juxtacanalicular region of the meshwork. Studies were conducted to
test the hypothesis that a factor mediates this response and to
identify the factor.
methods. Human anterior segment organ cultures were subjected to laser treatment
using standard clinical parameters and were returned to culture for 8
hours. The resultant 8-hour–conditioned culture medium was then tested
for factor activity by evaluating its ability to produce two typical
trabecular responses to laser treatment, that is, to induce stromelysin
expression or to trigger cell division, when applied to fresh organ
cultures or to cell cultures. Confocal immunohistochemistry of the
laser-treated organ cultures and western immunoblot analysis of the
conditioned medium were used to evaluate changes in potential
candidates for the factor activity. The ability of the interleukin
(IL)-1 receptor antagonist (IL-1ra)– and of tumor necrosis factor
alpha (TNFα)–blocking antibodies to eliminate the stromelysin
induction was evaluated.
results. Medium conditioned for 8 hours induced typical trabecular cell division
in anterior segment organ cultures. Medium conditioned for 8 hours, but
not for 30 minutes, induced typical increases in stromelysin expression
in these organ cultures and in cell cultures. After 8 hours, both
trabecular cells in laser-treated organ cultures and in the conditioned
medium contained elevated levels of IL-1β and TNFα. The
laser-treated organ cultures contained elevated levels of IL-1α, but
it was not secreted into the medium. The ability of conditioned media
to induce stromelysin expression was partially blocked by either the
IL-1ra– or the TNFα–blocking antibody.
conclusions. Laser trabeculoplasty induces the expression and secretion of both
IL-1β and TNFα within the first 8 hours after treatment. These
cytokines then mediate increased trabecular stromelysin expression.
Putatively, this initiates remodeling of the juxtacanalicular
extracellular matrix, a likely site for the aqueous outflow resistance,
and thus restores normal outflow facility.
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