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1 From the Department of Anatomy and Cell Biology, University of North Dakota School of Medicine and Health Sciences, Grand Forks; and the 2 Department of Biological Science and Disease, New England College of Optometry, Boston, Massachusetts.
PURPOSE. The rate of proteoglycan synthesis was measured in the scleras of adolescent marmosets that had undergone monocular form deprivation to characterize the scleral extracellular matrix changes associated with the development of myopia in a mature primate.
METHODS. Form deprivation myopia was induced in adolescent marmosets by unilateral lid suture for an average of 108 days. After the lids were reopened, the axial lengths and refractions were measured at intervals for up to 39 weeks. At the end of the study period, sclera were isolated and immediately radiolabeled with 35SO4 in organ culture. Proteoglycan synthesis rates were determined by measurement of 35SO4 incorporation into cetylpyridinium chlorideprecipitable glycosaminoglycans after digestion of the scleral samples with proteinase K. Collagen content was determined by measurement of total hydroxyproline in scleral digests. Newly synthesized proteoglycans were separated on a Sepharose CL-4B molecular sieve column and identified by their core proteins by Western blot analyses.
RESULTS. Lid suture resulted in myopia due to a significant increase in vitreous
chamber depth. After Sepharose CL-4B chromatography, newly synthesized
scleral proteoglycans isolated from normal, form-deprived, and
contralateral control eyes, resolved into one major peak that eluted in
the position of decorin, a small chondroitin-dermatan sulfate
proteoglycan. After digestion of the major peak with chondroitinase
ABC, an approximately 45-kDa core protein was detected by Western blot
analyses, confirming the presence of decorin. Form deprivation resulted
in a significant reduction in the rate of proteoglycan synthesis in the
posterior sclera (-43.55%, P
0.001).
Proteoglycan synthesis was also significantly reduced in the posterior
sclera of form-deprived eyes relative to total collagen content
(-36.19%, P
0.01) and was negatively
correlated with the rate of vitreous chamber elongation in the deprived
eye (r2 = 0.779, P
0.05).
CONCLUSIONS. Significant extracellular matrix remodeling occurs in the posterior sclera of the adolescent primate eye during vitreous chamber elongation and myopia development. The negative correlation between vitreous chamber elongation rates and the synthesis rates of decorin in form-deprived eyes suggests that proteoglycan synthesis within the posterior sclera plays a role in the regulation of ocular size and refraction in the adolescent marmoset.
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