Regulation of the biphasic decline in scleral proteoglycan synthesis during the recovery from induced myopia

Abstract

During the recovery from form deprivation myopia (myopic defocus), the rate of proteoglycan synthesis in the posterior sclera decreases co-incident with a deceleration of axial elongation. The choroid has been implicated in the regulation of scleral proteoglycan synthesis, possibly through the synthesis and secretion of scleral growth inhibitors. Therefore these studies were carried out to attempt to establish a causal relationship between choroidal secretion and the inhibition of scleral proteoglycan synthesis during the recovery from induced myopia. Chicks were form vision deprived for 10 days followed by a recovery period (3 h–20 days) of unrestricted vision. Sclera and choroids (5 mm punches) were isolated from control and treated eyes. The rate of proteoglycan synthesis was estimated by the incorporation of 35c in cetylpyridinium chloride-precipitable glycosaminoglycans by isolated sclera of control and treated eyes. Additionally, choroids from control and treated eyes were placed in co-culture with untreated age-matched normal chick sclera for 20–24 h, after which time sclera were removed and scleral proteoglycan synthesis rates were determined. Following removal of occluders, a biphasic decline was observed in scleral proteoglycan synthesis: A rapid decline in proteoglycan synthesis (−7.6% per hr; r2 = 0.923) was observed over the first 12 h of recovery, followed by a slow decline extending from 12 to 96 h (−0.3% per hr; r2 = 0.735). Proteoglycan synthesis rates gradually increased to control levels over the next 96 h at a rate of +0.3% per hr. No relative proteoglycan inhibition was observed when untreated sclera were co-cultured with choroids from eyes recovering for 0–4 days, whereas co-culture of untreated sclera with choroids from eyes recovering for 5 and 8 days resulted in significant inhibition of sclera proteoglycan synthesis, relative to that of sclera co-cultured with choroids from control eyes (≈−24%, P < 0.05, paired t-test). In conclusion, recovery from induced myopia is characterized by a rapid decline in proteoglycan synthesis which occurs within the first 12 h of unrestricted vision as a well as a slower more gradual decline that occurs over the next four days. Choroidal inhibition of scleral proteoglycan synthesis in vitro occurs during the second phase of decline and is most likely related to increased choroidal permeability; whereas the rapid decline in proteoglycan synthesis that occurs during the first 12 h of recovery is regulated by an independent, yet to be identified mechanism.