Investigating mechanisms of myopia in mice.

Genetic and environmental factors have been shown to control visually-guided eye growth and influence myopia development. However, investigations into the intersection of these two factors in controlling refractive development have been limited by the lack of a genetically modifiable animal model. Technological advances have now made it possible to assess refractive state and ocular biometry in the small mouse eye and therefore to exploit the many genetic mouse mutants to investigate mechanisms of visually-guided eye growth. This review considers the benefits and challenges of studying refractive development in mice, compares the results of refractive error and ocular biometry from wild-type strains and genetic models in normal laboratory visual environments or with disrupted visual input, and discusses some of the remaining challenges in interpreting data from the mouse to validate and standardize methods between labs.

[1]  S. Saw,et al.  Myopia: gene-environment interaction. , 2000, Annals of the Academy of Medicine, Singapore.

[2]  M. Edwards,et al.  Animal models of myopia. A review. , 2009, Acta ophthalmologica Scandinavica.

[3]  R. Beuerman,et al.  Expression of muscarinic receptors in human and mouse sclera and their role in the regulation of scleral fibroblasts proliferation , 2009, Molecular vision.

[4]  R. Beuerman,et al.  Molecular mechanisms of muscarinic receptors in mouse scleral fibroblasts: Prior to and after induction of experimental myopia with atropine treatment , 2011, Molecular vision.

[5]  C. Scharfe,et al.  The complete form of X-linked congenital stationary night blindness is caused by mutations in a gene encoding a leucine-rich repeat protein , 2000, Nature Genetics.

[6]  S. Crewther,et al.  Refractive compensation to optical defocus depends on the temporal profile of luminance modulation of the environment , 2002, Neuroreport.

[7]  K. Schmid,et al.  Contrast and spatial-frequency requirements for emmetropization in chicks , 1997, Vision Research.

[8]  Earl L. Smith,et al.  Recovery from form-deprivation myopia in rhesus monkeys. , 2004, Investigative ophthalmology & visual science.

[9]  C. S. Lam,et al.  Prevalence of Myopia in Local and International Schools in Hong Kong , 2004, Optometry and vision science : official publication of the American Academy of Optometry.

[10]  D. Yilmazer-Hanke Morphological correlates of emotional and cognitive behaviour: insights from studies on inbred and outbred rodent strains and their crosses , 2008, Behavioural pharmacology.

[11]  S. Sherman,et al.  Myopia in the lid-sutured tree shrew (Tupaia glis) , 1977, Brain Research.

[12]  Yimin Shen,et al.  Analysis of postnatal eye development in the mouse with high-resolution small animal magnetic resonance imaging. , 2010, Investigative ophthalmology & visual science.

[13]  F. Schaeffel Test systems for measuring ocular parameters and visual function in mice. , 2008, Frontiers in bioscience : a journal and virtual library.

[14]  Jun Liu,et al.  Vision-guided ocular growth in a mutant chicken model with diminished visual acuity. , 2012, Experimental eye research.

[15]  Tatsuo Itakura,et al.  Single-shot dimension measurements of the mouse eye using SD-OCT. , 2012, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye.

[16]  S. McFadden,et al.  Retinoic acid signals the direction of ocular elongation in the guinea pig eye , 2004, Vision Research.

[17]  H. Howland,et al.  Constant light produces severe corneal flattening and hyperopia in chickens , 1995, Vision Research.

[18]  J. Boatright,et al.  Exaggerated eye growth in IRBP-deficient mice in early development. , 2011, Investigative ophthalmology & visual science.

[19]  F. Schaeffel,et al.  Microarray analysis of retinal gene expression in Egr-1 knockout mice , 2008, Molecular vision.

[20]  W Neil Charman,et al.  Keeping the world in focus: how might this be achieved? , 2011, Optometry and vision science : official publication of the American Academy of Optometry.

[21]  F. Ferris,et al.  Increased prevalence of myopia in the United States between 1971-1972 and 1999-2004. , 2009, Archives of ophthalmology.

[22]  C. Wildsoet,et al.  The role of the retinal pigment epithelium in eye growth regulation and myopia: A review , 2005, Visual Neuroscience.

[23]  Gene P. Sackett,et al.  Visual acuity and visual responsiveness in dark-reared monkeys (Macaca nemestrina) , 1976, Vision Research.

[24]  Josh Wallman,et al.  The multifunctional choroid , 2010, Progress in Retinal and Eye Research.

[25]  P. E. Hallett,et al.  A schematic eye for the mouse, and comparisons with the rat , 1985, Vision Research.

[26]  S. John,et al.  Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection. , 2008, Progress in brain research.

[27]  Y. Rotenstreich,et al.  Cone-rod dystrophy and a frameshift mutation in the PROM1 gene , 2009, Molecular vision.

[28]  Susana Marcos,et al.  Optical aberrations in the mouse eye , 2006, Vision Research.

[29]  P. de la Villa,et al.  Refractive changes induced by form deprivation in the mouse eye. , 2003, Investigative ophthalmology & visual science.

[30]  F. Schaeffel,et al.  Defocus-induced changes in ZENK expression in the chicken retina. , 2002, Investigative ophthalmology & visual science.

[31]  J. Larsen AXIAL LENGTH OF THE EMMETROPIC EYE AND ITS RELATION TO THE HEAD SIZE , 1979, Acta ophthalmologica.

[32]  Robert W. Williams,et al.  Eye, retina, and visual system of the mouse , 2008 .

[33]  M. A. Ali,et al.  Vision in Vertebrates , 1985, Springer US.

[34]  Neville A. McBrien,et al.  The development of experimental myopia and ocular component dimensions in monocularly lid-sutured tree shrews (Tupaia belangeri) , 1992, Vision Research.

[35]  R. Williams,et al.  Eye1 and Eye2: gene loci that modulate eye size, lens weight, and retinal area in the mouse. , 1999, Investigative ophthalmology & visual science.

[36]  J. Jonas,et al.  Ocular Axial Length and Its Associations in Chinese: The Beijing Eye Study , 2012, PloS one.

[37]  R. Williams,et al.  Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice. , 2001, Molecular vision.

[38]  C. S. Lam,et al.  The epidemiology of myopia in Hong Kong. , 2004, Annals of the Academy of Medicine, Singapore.

[39]  F. Schaeffel,et al.  Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision , 2007, Graefe's Archive for Clinical and Experimental Ophthalmology.

[40]  S. McFadden,et al.  Form-deprivation myopia in the guinea pig (Cavia porcellus) , 2006, Vision Research.

[41]  P. Sieving,et al.  Refractive errors of retinitis pigmentosa patients. , 1978, The British journal of ophthalmology.

[42]  Vittorio Porciatti,et al.  Postnatal elongation of eye size in DBA/2J mice compared with C57BL/6J mice: in vivo analysis with whole-eye OCT. , 2011, Investigative ophthalmology & visual science.

[43]  D. Mutti,et al.  The Artifact of Retinoscopy Revisited: Comparison of Refractive Error Measured by Retinoscopy and Visual Evoked Potential in the Rat , 1997, Optometry and Vision Science.

[44]  M. Pardue,et al.  Assessment of Axial Length Measurements in Mouse Eyes , 2012, Optometry and vision science : official publication of the American Academy of Optometry.

[45]  J. Siegwart,et al.  Steady state mRNA levels in tree shrew sclera with form-deprivation myopia and during recovery. , 2001, Investigative ophthalmology & visual science.

[46]  J. Sivak,et al.  Inducing form-deprivation myopia in fish. , 2005, Investigative ophthalmology & visual science.

[47]  J. Erichsen,et al.  Common determinants of body size and eye size in chickens from an advanced intercross line. , 2009, Experimental eye research.

[48]  R. Stone,et al.  Gene profiling in experimental models of eye growth: Clues to myopia pathogenesis , 2010, Vision Research.

[49]  J. Qu,et al.  Axial myopia induced by hyperopic defocus in guinea pigs: A detailed assessment on susceptibility and recovery. , 2009, Experimental eye research.

[50]  Frank Schaeffel,et al.  A paraxial schematic eye model for the growing C57BL/6 mouse , 2004, Vision Research.

[51]  S. Crewther,et al.  Low frequency temporal modulation of light promotes a myopic shift in refractive compensation to all spectacle lenses. , 2006, Experimental eye research.

[52]  R. Beuerman,et al.  Evaluation of gene expression profiles and pathways underlying postnatal development in mouse sclera , 2012, Molecular vision.

[53]  M. R. Hoffman,et al.  Sonic Hedgehog Expression and Its Role in Form-Deprivation Myopia in Mice , 2009, Current eye research.

[54]  J. Qu,et al.  Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera , 2012, Molecular vision.

[55]  S. Crewther,et al.  Changes in eye growth produced by drugs which affect retinal ON or OFF responses to light. , 1996, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.

[56]  F. Schaeffel The Mouse Model of Myopia , 2010 .

[57]  Meixiao Shen,et al.  Biometric measurement of the mouse eye using optical coherence tomography with focal plane advancement , 2008, Vision Research.

[58]  N. Whittock,et al.  Phenotype of autosomal dominant cone–rod dystrophy due to the R838C mutation of the GUCY2D gene encoding retinal guanylate cyclase-1 , 2007, Eye.

[59]  Jianhua Wang,et al.  The development of the refractive status and ocular growth in C57BL/6 mice. , 2008, Investigative ophthalmology & visual science.

[60]  David R. Williams,et al.  Optical properties of the mouse eye , 2011, Biomedical optics express.

[61]  F. Schaeffel,et al.  A microarray analysis of retinal transcripts that are controlled by image contrast in mice , 2007, Molecular vision.

[62]  J. Siegwart,et al.  Goggles for controlling the visual environment of small animals. , 1994, Laboratory animal science.

[63]  Eric P.H. Yap,et al.  Two models of experimental myopia in the mouse , 2008, Vision Research.

[64]  Jonathan Winawer,et al.  Homeostasis of Eye Growth and the Question of Myopia , 2012, Neuron.

[65]  Searle Ag Comparative genetics of albinism , 1990 .

[66]  W. Drexler,et al.  Heritability of ocular component dimensions in mice phenotyped using depth-enhanced swept source optical coherence tomography. , 2011, Experimental eye research.

[67]  F. Schaeffel,et al.  Regulation of Egr-1, VIP, and Shh mRNA and Egr-1 protein in the mouse retina by light and image quality. , 2005, Molecular vision.

[68]  S. Crewther,et al.  Inhibition of retinal ON/OFF systems differentially affects refractive compensation to defocus , 2003, Neuroreport.

[69]  M. Angelis,et al.  Variations of eye size parameters among different strains of mice , 2006, Mammalian Genome.

[70]  S. McFadden,et al.  Spectacle lens compensation in the pigmented guinea pig , 2009, Vision Research.

[71]  Earl L. Smith,et al.  Spectacle lenses alter eye growth and the refractive status of young monkeys , 1995, Nature Medicine.

[72]  Machelle T. Pardue,et al.  Head-mounted goggles for murine form deprivation myopia , 2007, Journal of Neuroscience Methods.

[73]  T. T. Norton,et al.  Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery. , 2005, Investigative ophthalmology & visual science.

[74]  J. Siegwart,et al.  Perspective: how might emmetropization and genetic factors produce myopia in normal eyes? , 2011, Optometry and vision science : official publication of the American Academy of Optometry.

[75]  R. Stone,et al.  Photoperiod, early post-natal eye growth, and visual deprivation , 1995, Vision Research.

[76]  D. Ingram,et al.  An overview of neurobiological comparisons in mouse strains , 1980, Neuroscience & Biobehavioral Reviews.

[77]  Robert W. Williams,et al.  High susceptibility to experimental myopia in a mouse model with a retinal on pathway defect. , 2008, Investigative ophthalmology & visual science.

[78]  Frank Schaeffel,et al.  In vivo biometry in the mouse eye with low coherence interferometry , 2004, Vision Research.

[79]  Tatiana V. Tkatchenko,et al.  Ketamine–xylazine anesthesia causes hyperopic refractive shift in mice , 2010, Journal of Neuroscience Methods.

[80]  J. Qu,et al.  Relative Axial Myopia Induced by Prolonged Light Exposure in C57BL/6 Mice , 2010, Photochemistry and photobiology.

[81]  A. Searle Comparative genetics of albinism. , 1990, Ophthalmic paediatrics and genetics.

[82]  R. Douglas,et al.  Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. , 2004, Investigative ophthalmology & visual science.

[83]  T. T. Norton,et al.  Patterns of mRNA and protein expression during minus-lens compensation and recovery in tree shrew sclera , 2011, Molecular vision.

[84]  L. Akileswaran,et al.  Localization of nyctalopin in the mammalian retina , 2006, The European journal of neuroscience.

[85]  R. Williams,et al.  Mouse models for the analysis of myopia: an analysis of variation in eye size of adult mice. , 1999, Optometry and vision science : official publication of the American Academy of Optometry.

[86]  Robert W. Williams,et al.  Measurement of Refractive State and Deprivation Myopia in Two Strains of Mice , 2004, Optometry and vision science : official publication of the American Academy of Optometry.

[87]  J Turkel,et al.  Extreme myopia produced by modest change in early visual experience. , 1978, Science.

[88]  John C Morrison,et al.  Pathophysiology of human glaucomatous optic nerve damage: insights from rodent models of glaucoma. , 2011, Experimental eye research.

[89]  J K Lauber,et al.  Dimensional and Physiological Lesions in the Chick Eye as Influenced by the Light Environment 1 , 1975, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[90]  Hirohiko Kakizaki,et al.  Prevalence of myopia and its association with body stature and educational level in 19-year-old male conscripts in seoul, South Korea. , 2012, Investigative ophthalmology & visual science.

[91]  J. Tuo,et al.  Effects of Flickering Light on Refraction and Changes in Eye Axial Length of C57BL/6 Mice , 2011, Ophthalmic Research.

[92]  S. Jacobson,et al.  Mutations in NYX, encoding the leucine-rich proteoglycan nyctalopin, cause X-linked complete congenital stationary night blindness , 2000, Nature Genetics.

[93]  J. Qu,et al.  Axial myopia induced by a monocularly-deprived facemask in guinea pigs: A non-invasive and effective model. , 2006, Experimental eye research.

[94]  M. He,et al.  Longitudinal changes of axial length and height are associated and concomitant in children. , 2011, Investigative ophthalmology & visual science.

[95]  M. Millodot,et al.  Retinoscopy and Eye Size , 1970, Science.

[96]  F. Schaeffel,et al.  Relative axial myopia in Egr-1 (ZENK) knockout mice. , 2007, Investigative ophthalmology & visual science.

[97]  T H Roderick,et al.  Essential iris atrophy, pigment dispersion, and glaucoma in DBA/2J mice. , 1998, Investigative ophthalmology & visual science.

[98]  T. M. Esdaille,et al.  Dark Light, Rod Saturation, and the Absolute and Incremental Sensitivity of Mouse Cone Vision , 2010, The Journal of Neuroscience.

[99]  K. Yagasaki,et al.  Congenital stationary night blindness with negative electroretinogram. A new classification. , 1986 .

[100]  S. Judge,et al.  Ocular development and visual deprivation myopia in the common marmoset (Callithrix jacchus) , 1993, Vision Research.

[101]  Jianhua Wang,et al.  Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice. , 2010, Investigative ophthalmology & visual science.

[102]  W. Stell,et al.  Flicker downregulates the content of crystallin proteins in form-deprived C57BL/6 mouse retina. , 2012, Experimental eye research.

[103]  Yimin Shen,et al.  Mouse experimental myopia has features of primate myopia. , 2010, Investigative ophthalmology & visual science.

[104]  T. Wiesel,et al.  Myopia and eye enlargement after neonatal lid fusion in monkeys , 1977, Nature.

[105]  J. Boatright,et al.  Non-contact measurement of linear external dimensions of the mouse eye , 2010, Journal of Neuroscience Methods.

[106]  J. Rada,et al.  The sclera and myopia. , 2006, Experimental eye research.