Friday, April 26, 2024
4/26/2024
During postnatal development when the eye is still growing, an “emmetropization mechanism” uses the eye’s refractive error to regulate the growth of the scleral shell to match the axial length of the eye to the focal plane. Despite this, in over 40% of Americans and up to 96% of groups in East Asia, the eye becomes too long for its own optics and is thus myopic. Even low amounts of myopia raise the risk of developing blinding conditions and refractive surgery does not change this. Thus, effective strategies to slow eye growth and reduce the prevalence of myopia are needed. Maintenance of emmetropia is a neglected area of research. Most myopic children emmetropize relatively normally, but then are unable to maintain emmetropia in the longer maintenance phase of emmetropia. Our research in tree shrews (cone-dominated dichromatic mammals closely related to primates) has shown that maintaining emmetropia is an active process throughout adolescence. Is the eye becoming too short (hyperopia) and should increase its growth rate to maintain emmetropia (retinal GO signals are needed), or is it becoming too long (myopia) and should slow the axial elongation rate to maintain emmetropia (retinal STOP signals are needed). An important problem is that we do not have a solid understanding of the visual cues used by the emmetropization mechanism to generate STOP signals that will prevent eyes from becoming too long. In tree shrews, we have discovered that exposure to narrow-band long wavelength (red) light (which only stimulates the long-wavelength sensitive, or LWS, cones) seems to generate STOP signals that slow growth during the maintenance phase of emmetropization. In specific aim 1, we will determine the optimal parameters for the red light to generate the maximum STOP signal with minimal exposure and learn if red-light STOP signals show non-linear summation, similar to other stimuli that generate STOP signals (myopic defocus or interrupted minus-lens wear). In specific aim 2, we will determine if the red light “treatment” can produce consistent STOP signaling over a long period of time in the maintenance phase of emmetropization. We will also examine if the red light can counteract the myopiagenic effects of a minus lens in a paradigm similar to that used in myopia-control studies. In specific aim 3, we will use both analysis of retinal dopamine, and of gene expression in the retina and post-retinal signaling cascade, to determine if red-light STOP signals act via the same pathways as other STOP stimuli (such as recovery from induced myopia), or if the pathways are parallel and novel. The knowledge gained from this project will not only generate critical data on the operation of the emmetropization mechanism during the maintenance phase, but also may result in the development of red light as a novel anti-myopia therapy.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
