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Treatment
1 From the Glaucoma Center and the Department of Ophthalmology, University of California San Diego, La Jolla; the 2 Department of Ophthalmology, University of California San Francisco; and the 3 Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison.
PURPOSE. Mutations in the trabecular meshwork inducible glucocorticoid response (TIGR) gene, also known as myocilin, have recently been linked to some forms of glaucoma. Recent studies have shown that TIGR protein also is expressed in the ciliary muscle. Because uveoscleral outflow, which traverses the ciliary muscle, is increased by prostaglandins (PGs), the present study assessed whether topical PGs alter the amount of TIGR protein within the ciliary muscle.
METHODS. Vehicle was topically applied to one eye, and 2 µg
PGF2
-isopropyl ester (PGF2-IE) was
applied to the other eye of cynomolgus monkeys twice daily for 5 days.
Pressure reductions of 5 mm Hg in the PGF2-IE–treated
eyes were confirmed. The eyes were then fixed and paraffin sections
were cut from each eye. The distribution of TIGR protein in the ciliary
muscle was determined by confocal scanning laser microscopy. Additional
sections were immunostained with a polyclonal antibody to recombinant
TIGR protein or with a polyclonal antibody to a synthetic peptide
corresponding to the leucine zipper region within the TIGR protein.
Staining intensity in the ciliary muscle was assessed by measuring
optical density (OD) along two line segments overlying the ciliary
muscle, by using a high-resolution imaging densitometer.
RESULTS. TIGR protein immunoreactivity was observed in ciliary muscle fibers
throughout the ciliary muscle. Extracellular TIGR immunoreactivity
colocalized with collagen type IV immunoreactivity. Intracellular
staining also was present. Immunoreactivity was less intense in the
sections from the PGF2-IE–treated eyes compared with
the vehicle-treated eyes. This was reflected in the reduction of mean
OD scores in each monkey. Overall, the reduction of mean OD scores in
the treated eyes was 42.1% ± 9.9% (P < 0.005)
with the anti-recombinant TIGR antibody and 27.3% ± 10.4% with the
anti-TIGR peptide antibody (P < 0.005).
CONCLUSIONS. TIGR protein immunoreactivity was present both intracellularly and
extracellularly in the ciliary muscle of the cynomolgus monkey. This
suggests that extracellular TIGR protein is in contact with aqueous
humor in the uveoscleral outflow pathway. Moreover, IOP-lowering
topical PGF2-IE treatment decreases the amount of TIGR
protein in the ciliary muscle.
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