Scleral remodelling in myopia and its manipulation: a review of recent advances in scleral strengthening and myopia control

Abstract

The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.

Systematic Analysis of Transcriptomic Profile of the Effects of Low Dose Atropine Treatment on Scleral Fibroblasts using Next-Generation Sequencing and Bioinformatics

“…Scleral remodeling occurs as a consequence of increases in cell differentiation changes during myopia development 2,70. This view is supported by in vivo studies that hypoxia-inducible factor-1 α ( HIF-1α ) was upregulated in the myopic sclera, which promoted myopia through fibroblast-to-myofibroblast transdifferentiation.…”

“…We report for the first time, utilizing NGS for human scleral miRNA and mRNA expression profiling upon treatment with atropine. As the sclera defines the final ocular shape and size, the sclera has become an appealing targeting tissue for myopia control 1,2. Preventing the onset of myopia and setting back its progression in early life are vital steps in management of myopia.…”

“…Reduced production of new ECM is a result of decreased levels of collagen synthesis, particularly type I collagen, and diminished production of proteoglycans and their GAG side chains 12. At a morphological level, high myopic eyes have collagen fibers of smaller diameter, and fewer collagen fiber bundles 2,79. Atropine was shown to inhibit GAG synthesis in scleral fibroblasts via a nonmuscarinic mechanism 80.…”

“…The scleral structure is predominantly made up of collagen, and interwoven fibroblasts that are responsible for the regulation and production of the extracellular matrix (ECM). Enzymes that are responsible for the remodeling of the ECM, including matrix metalloproteinases (MMPs) and tissue inhibitor of metallopreoteinase (TIMP) families, and a wide variety of cytokines and signaling molecules, are important to homeostasis of the sclera 2,3.…”

“…A considerable amount of effort has been devoted to understanding the biomechanical and genetic regulators in ocular growth, and preventing excessive growth of the eye 10-12. The development of myopia is accompanied by increased scleral matrix remodeling, including scleral thinning, fibril disassembly, and reduced glycosaminoglycan (GAG) and collagen content 2,13. Therefore, disrupting the scleral remodeling process may allow us to retard, or even prevent excessive ocular growth.…”