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Jody A. Rada, Cheryll A. Perry, Michelle L. Slover, Virginia R. Achen; Gelatinase A and TIMP-2 Expression in the Fibrous Sclera of Myopic and Recovering Chick Eyes. Invest. Ophthalmol. Vis. Sci. 1999;40(13):3091-3099.
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purpose. Myopia, or nearsightedness, is characterized by excessive lengthening
of the ocular globe and is associated with extracellular matrix
remodeling in the posterior sclera. The activity of gelatinase A, a
member of the matrix metalloproteinase family, has been shown to
increase in the posterior sclera during the development of induced
myopia in several species. In the present study, the distribution and
relative expression of gelatinase A and its associated inhibitor,
tissue inhibitor of metalloproteinases (TIMP)-2, were measured within
the fibrous scleras of experimentally myopic (form-deprived) eyes,
control eyes, and eyes recovering from form deprivation to better
understand the mechanisms that regulate scleral remodeling and the rate
of ocular elongation.
methods. Total RNA was extracted from the posterior scleras of form-deprived
chick eyes, eyes recovering from deprivation myopia, and paired
contralateral control eyes, and subjected to northern blot analysis
analyses using cDNA probes to chicken gelatinase A and TIMP-2. The
distribution of gelatinase A and TIMP-2 mRNAs was evaluated by in situ
hybridization on frozen sections of chick scleras using 33P-labeled RNA probes. Gelatinase A activity within the
fibrous scleras of form-deprived eyes and paired contralateral
recovering eyes was evaluated by gelatin zymography.
results. Northern blot analysis indicated that the relative expression of
gelatinase A was increased by 128% in deprived eyes
(P = 0.009), whereas after 1 day of recovery,
levels were decreased by 80% in scleras from recovering eyes
(P = 0.005). In contrast, TIMP-2 expression was
significantly decreased (−53%, P = 0.027) in the
posterior scleras of form-deprived eyes. No significant differences
were detected in levels of TIMP-2 expression between recovering eyes
and paired control eyes. In situ hybridization indicated that most of
the gelatinase A transcripts were present in the fibrous layer of the
posterior scleras from form-deprived and recovering eyes.
conclusions. Changes in the steady state levels of gelatinase A and TIMP-2 mRNA lead
to changes in gelatinase activity within the fibrous sclera and
mediate, at least in part, the process of visually regulated ocular
growth and scleral remodeling.
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