Mechanisms of Ocular Development

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications & trials

Abstract

Principal Investigator/Program Director (Last, first, middle): Norton, Thomas, T. Project Summary/Abstract The goal of this project is to understand the emmetropization mechanism that uses visual signals to match the axial length of juvenile eyes to their optical power. This mechanism usually produces eyes with little refractive error. However, a significant proportion of the U.S. population develops refractive errors, especially myopia, which suggests variability in the functioning of the emmetropization mechanism. In high myopia, the excessive length of the eye (which is not corrected by optical treatments, including refractive surgery) is a risk factor for retinal detachment and glaucoma, making myopia the 7th leading cause of blindness in the U.S. The emmetropization mechanism has at least three main components: 1) the retina, which detects the amount of defocus (or other visual cues); 2) a signaling cascade from the retina, through the retinal pigment epithelium (RPE) and choroid, to the sclera (the fibrous outer coat of the eye); and 3) fibroblasts in the sclera which respond to retinal signals by regulating the axial length. Our working hypothesis is that retinally-derived signals control the remodeling of the scleral extracellular matrix, which in turn controls scleral extensibility, axial elongation, and refractive state. In the previous project period, we identified experimental paradigms in which similar visual stimuli produce different eye-growth responses due to the prior history of the eye (longer or shorter than normal, an [unreadable]eye-size[unreadable] factor) that may model some aspects of the variable response of human eyes to myopiagenic environmental conditions. Specific Aims 1 and 2 will use these dissociative paradigms to determine whether the source of the variability can be localized to the sclera, retina, or both and to identify the specific retinal and scleral gene-expression changes that are responsible. Of the gene-expression changes identified previously in the retina and sclera, it is unclear which are essential parts of the mechanism. Specific Aim 3 will use three different methods of inducing myopia (darkness, form deprivation, and minus-lens wear) to identify components of the retinal and scleral gene expression that are common to all three and therefore likely to be the essential changes for the control of axial elongation. At the conclusion of the proposed studies we will know 1) the constellation of changes associated with retinal [unreadable]go[unreadable] and [unreadable]stop[unreadable] signals and scleral [unreadable]stop[unreadable] and [unreadable]go[unreadable] responses, 2) whether early restraint of axial elongation produces changes that are encoded in the sclera, the retina, or both and 3) if there is a unique constellation of retinal and scleral changes that occur in response to all three differing myopiagenic conditions. These studies will advance our understanding of the specific genes and gene products that control the axial elongation rate and, hence, refractive state. Understanding this mechanism may help explain why children born myopic, and who achieve emmetropia early in life, have a higher risk subsequently developing myopia. It may also lead to successful optical or pharmacological interventions to slow or prevent myopia. Project Description Page 6