Neonatal aphakia retards ocular growth and alters scleral geneexpression in rhesus monkeys

[摘要] Purpose: We hypothesize that remodeling of the scleral extracellularmatrix, involving collagen and proteoglycan synthesis and turnover, is akey process involved in ocular growth. Decreased axial elongation isobserved following neonatal removal of the crystalline lens in a rhesusmonkey model of congenital cataract. We wanted to determine changes ingene expression in the operated and companion eye following lensectomy,especially for extracellular matrix in the sclera.Methods: Between 4 and 7 days of age, infant monkeys underwentsurgical removal of the lens from the right eye. Axial lengths of theoperated and unmanipulated fellow eyes were measured and wheninterocular differences of >0.4 mm were achieved, monkeys weresacrificed and RNA was isolated from sclera. In order to determinechanges in scleral gene expression in aphakic versus control eyes, weused Clontech's Atlas Gene Array (Human Cancer Array version 1.2)hybridized with total RNA from three monkeys.Results: Atlas Gene Array analysis demonstrated differentialexpression of several genes in the operated versus the unmanipulatedeye. Most notably, there was a statistically significant increase inexpression of several extracellular matrix (ECM) genes including:aggrecan, decorin, biglycan, several collagens, and tenascin in the RNAfrom the sclera of the aphakic eyes when compared to the unmanipulatedeyes. Genes for several matrix metalloproteinases (MMPs) showed nosignificant change following lens removal although there was a trendtowards decreased expression. There were also statistically significantchanges in the pattern of gene expression in the operated eye relativeto the unmanipulated eye for cell adhesion, cell cycle, apoptosis, andcytoskeleton transcripts.Conclusions: Our results suggest that removal of the crystallinelens alters gene expression in the sclera with a prominent upregulationof ECM transcripts. These data support recent evidence that remodelingof the ECM composition of the sclera may be an important regulator ofocular growth.

[学科分类] 生物化学/生物物理