Scleral Extracellular Matrix Research Articles

The Circadian Rhythm in Intraocular Pressure and its Relation to Diurnal Ocular Growth Changes in Chicks

Recent investigations have shown that growing chicken eyes elongate during the day and shorten during the night. We asked whether the chick, like a number of other animals, exhibits a rhythm in intraocular pressure (IOP) and whether this rhythm might be associated with this rhythm in elongation. We find that the intraocular pressure in normal eyes is high during the day and low in the middle of the night, similar to the rhythm in ocular elongation. The amplitude of this rhythm in IOP is approximately 8 mm Hg; it persists in constant darkness, albeit with a reduced amplitude, implying that the rhythm has a circadian component. Form deprivation by translucent diffusers does not affect the amplitude of the rhythm in IOP, but makes the phase of the rhythm more variable, such that the trough no longer consistently occurs at night.We find that the magnitude of the ocular compliance (the change in length induced by change in intraocular pressure) is consistent with the possibility that the diurnal changes in IOP might, through mechanical stretch, account for much of the diurnal changes in length. However, in individual eyes, we find consistent phase differences between the rhythms in IOP and ocular elongation. Therefore, we propose that the rhythm in IOP influences ocular elongation in ways other than by simply inflating the eye, for example, by influencing underlying rhythms in scleral extracellular matrix production. We conclude that the rhythm in IOP plays a role in the regulation of the growth of the eye.

Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid

PURPOSE. It has been demonstrated that chick eye growth compensates for defocus imposed by spectacle lenses: the eye elongates in response to hyperopic defocus imposed by negative lenses and slows its elongation in response to myopic defocus imposed by positive lenses. We ask whether the synthesis of scleral extracellular matrix, specifically glycosaminoglycans, changes in parallel with the changes in ocular elongation. In addition, there is a choroidal component to compensation for spectacle lenses; the choroid thickens in response to myopic defocus and thins in response to hyperopic defocus. We ask whether choroidal glycosaminoglycan synthesis changes in parallel with changes in choroidal thickness. METHODS. Chicks wore either a +15 diopter (D) or -15 D spectacle lens over one eye, or they wore one lens of each power over each eye for 5 days. At the end of this period, we measured refractive errors and ocular dimensions by refractometry and A-scan ultrasonography, respectively. Pieces of the scleras and choroids from these eyes were put into culture and the synthesis of glycosaminoglycans was assessed by measuring the incorporation of radioactive inorganic sulfur. RESULTS. We here report that the compensatory modulation of the length of the eye involves changes in the synthesis of glycosaminoglycans in the sclera, with synthesis increasing in eyes wearing -15 D spectacles lenses and decreasing in eyes wearing +15 D lenses. In addition, changes in the synthesis of glycosaminoglycans in the choroid are correlated with changes in choroidal thickness: eyes wearing +15 D lenses develop thicker choroids and these choroids synthesize more glycosaminoglycans than choroids from eyes wearing -15 D lenses. CONCLUSIONS. Changes in scleral glycosaminoglycan synthesis accompany lens-induced changes in the length of the eye. Furthermore, changes in the thickness of the choroid are also associated with changes in the synthesis of glycosaminoglycans. These results are consistent with the regulation of the growth of the eye being bidirectional, and with the retina being able to sense the sign of defocus.

Reduced extracellular matrix in mammalian sclera with induced myopia

The purpose of this study was to learn whether visual form deprivation, which produces myopia in the deprived eye, alters the scleral extracellular matrix in tree shrew, a mammal closely related to primates. Axial myopia was induced in 10 tree shrews by monocular deprivation imposed with a translucent diffuser. The other eye in each animal was an untreated control. After 21 days of deprivation the refractive state and axial component dimensions were measured and the eyes were assayed for levels of DNA, hydroxyproline, and sulfated glycosaminoglycans (GAGs) in samples of the sclera and the cornea. In comparison to the open control eye, the deprived eyes became myopic and elongated. In the sclera, DNA levels were not significantly changed from the control eye. Sulfated GAG levels were significantly lower in the deprived eyes, as compared to the control eyes, at the posterior pole (-15.6%), at the nasal equatorial region (-18.1%), and in the rest of the sclera (-11.6%). The hydroxyproline level was significantly lower only at the posterior pole (-11.8%). Levels of sulfated GAGs were significantly reduced relative to DNA and relative to hydroxyproline in the total sclera. No significant changes were found in the cornea. The lower level of sulfated GAGs throughout the sclera of the deprived eyes, as compared with the control eyes, suggests that the deprived sclera contained less proteoglycan, or that the proteoglycans were less glycosylated or less sulfated. In contrast, the regional reduction of hydroxyproline suggests that collagen accumulation was specifically reduced only at the posterior pole of deprived eyes. These results suggest that form deprivation slows or reverses the normal process of extracellular matrix accumulation in the sclera of this mammal. This may allow the sclera to be more distensible, permitting the vitreous chamber elongation and resultant myopia.