Circadian rhythms, refractive development, and myopia

• Type of Material: Article
• Authors: Ranjay Chakraborty, Flinders University; Lisa A. Ostrin, University of Houston; Debora L. Nickla, New England College of Optometry; P Michael Iuvone, Emory University; Machelle Pardue, Emory University; Richard A. Stone, University of Pennsylvania
• Language: English
• Date: 2018-05-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 The Authors Ophthalmic & Physiological Optics © 2018 The College of Optometrists
• Final Published Version (URL): http://dx.doi.org/10.1111/opo.12453
• Title of Journal or Parent Work: Ophthalmic and Physiological Optics
• ISSN: 0275-5408
• Volume: 38
• Issue: 3
• Start Page: 217
• End Page: 245
• Grant/Funding Information: This work was supported by National Institutes of Health R01 EY016435 (MTP), R01 EY004864 (PMI), R01 EY027711 (PMI), P30 EY006360 (PMI), R01 EY022342 (RAS/PMI/MTP), EY001583 (RAS), EY013636 (DLN) and EY025307 (DLN); the Department of Veterans Affairs Research Career Scientist Award (MTP); Research to Prevent Blindness (RAS, PMI); Paul and Evanina Bell Mackall Foundation Trust (RAS).
• Keywords: ENDOGENOUS DOPAMINE RELEASE; INTRAOCULAR-PRESSURE FLUCTUATIONS; PIRENZEPINE OPHTHALMIC GEL; dopamine; APOLIPOPROTEIN-A-I; clock genes; STATIONARY NIGHT BLINDNESS; melanopsin; RETINAL GANGLION-CELLS; Ophthalmology; myopia; circadian rhythms; Science & Technology; Life Sciences & Biomedicine; EYE GROWTH; GROWTH-FACTOR BFGF; FORM-DEPRIVATION MYOPIA; refractive development; RHESUS-MONKEY RETINA
• Research Categories: Health Sciences, Opthamology; Engineering, Biomedical

Abstract

Purpose: Despite extensive research, mechanisms regulating postnatal eye growth and those responsible for ametropias are poorly understood. With the marked recent increases in myopia prevalence, robust and biologically-based clinical therapies to normalize refractive development in childhood are needed. Here, we review classic and contemporary literature about how circadian biology might provide clues to develop a framework to improve the understanding of myopia etiology, and possibly lead to rational approaches to ameliorate refractive errors developing in children. Recent findings: Increasing evidence implicates diurnal and circadian rhythms in eye growth and refractive error development. In both humans and animals, ocular length and other anatomical and physiological features of the eye undergo diurnal oscillations. Systemically, such rhythms are primarily generated by the ‘master clock’ in the surpachiasmatic nucleus, which receives input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) through the activation of the photopigment melanopsin. The retina also has an endogenous circadian clock. In laboratory animals developing experimental myopia, oscillations of ocular parameters are perturbed. Retinal signaling is now believed to influence refractive development; dopamine, an important neurotransmitter found in the retina, not only entrains intrinsic retinal rhythms to the light:dark cycle, but it also modulates refractive development. Circadian clocks comprise a transcription/translation feedback control mechanism utilizing so-called clock genes that have now been associated with experimental ametropias. Contemporary clinical research is also reviving ideas first proposed in the nineteenth century that light exposures might impact refraction in children. As a result, properties of ambient lighting are being investigated in refractive development. In other areas of medical science, circadian dysregulation is now thought to impact many non-ocular disorders, likely because the patterns of modern artificial lighting exert adverse physiological effects on circadian pacemakers. How, or if, such modern light exposures and circadian dysregulation contribute to refractive development is not known. Summary: The premise of this review is that circadian biology could be a productive area worthy of increased investigation, which might lead to the improved understanding of refractive development and improved therapeutic interventions.