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Pathological myopia (PM) is a leading cause of irreversible visual impairment worldwide, and efforts are dedicated to the study of its underlying mechanisms. Axial extension of the eyeball is regulated via a cascade of biochemical molecules that are initiated in the retina or choroid, causing scleral extracellular matrix (ECM) remodelling. Wnt/β-catenin signalling pathway is a growth control pathway that affects cell proliferation and architecture maintenance. Dickkopf-1 (DKK1) is a protein that antagonises this pathway and therefore regulates fibrosis and deposition of ECM molecules. Evidence has shown that gene therapy with DKK1 could suppress collagen accumulation and release of ECM in heart, renal and liver fibrosis. However, the possible roles of DKK1 in myopia are still poorly understood. The authors of this study evaluated DKK1 levels in the vitreous of 136 patients with no myopia, low to moderate myopia and PM and sought to explore the relationship with axial length, choroidal thickness and other cytokines. The intravitreous levels of DKK1 and matrix metalloproteinase-2 (MMP-2) were much higher in patients with PM than the other two groups. Other cytokines showed no obvious differences. There was also a close association between DKK1 levels and axial length, as well as subfoveal choroidal thickness (SFCT). The biomechanical properties of the sclera are dependent on composition of the ECM and remodelling of the sclera is under control of a specific cascade of biochemical events that are initially located in the retina, including DKK1. This study supports the hypothesis that altered biochemical factors in the intraocular fluids may be a reflection of retina-derived regulation of scleral remodelling through the release of molecules that could degrade various components of ECM, which leads to axial elongation in highly myopic eyes.

Increased levels of DKK1 in vitreous fluid of patients with pathological myopia and the correlation between DKK1 levels and axial length.
Peng M, Wei Y, Zhang Z, et al.
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Kurt Spiteri Cornish

Sheffield Teaching Hospitals NHS Trust, London, UK.

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