Decreased proteoglycan synthesis associated with form deprivation myopia in mature primate eyes

PURPOSE. The rate of proteoglycan synthesis was measured in the scleras of adolescent marmosets that had undergone monocular form deprivation to chara cterize the scleral extracellular matrix changes associated with the develo pment of myopia in a mature primate. METHODS. Form deprivation myopia was induced in adolescent marmosets by uni lateral 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 immediatel y radiolabeled with (SO4)-S-35 in organ culture. Proteoglycan synthesis rat es were determined by measurement of (SO4)-S-35 incorporation into cetylpyr idinium chloride-precipitable glycosaminoglycans after digestion of the scl eral samples with proteinase K. Collagen content was determined by measurem ent of total hydroxyproline in scleral digests. Newly synthesized proteogly cans were separated on a Sepharose CL-4B molecular sieve column and identif ied by their core proteins by Western blot analyses. RESULTS. Lid suture resulted in myopia due to a significant increase in vit reous chamber depth. After Sepharose CL-4B chromatography, newly synthesize d scleral proteoglycans isolated from normal, form-deprived, and contralate ral control eyes, resolved into one major peak that eluted in the position of decorin, a small chondroitin-dermatan sulfate proteoglycan. After digest ion 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 o f proteoglycan synthesis in the posterior sclera (-43.55%, P less than or e qual to 0.001). Proteoglycan synthesis was also significantly reduced in th e posterior sclera of form-deprived eyes relative to total collagen content (-36.19%, P less than or equal to 0.01) and was negatively correlated with the rate of vitreous chamber elongation in the deprived eye (r(2) = 0.779, P less than or equal to 0.05). CONCLUSIONS. Significant extracellular matrix remodeling occurs in the post erior sclera of the adolescent primate eye during vitreous chamber elongati on and myopia development. The negative correlation between vitreous chambe r elongation rates and the synthesis rates of decorin in form-deprived eyes suggests that proteoglycan synthesis within the posterior sclera plays a r ole in the regulation of ocular size and refraction in the adolescent marmo set.