Animal Models of Myopia: Learning How Vision Controls the Size of the Eye.

As they grow up, approximately 25% of children in the United States become myopic (nearsighted). A much smaller fraction become significantly hyperopic (farsighted), while the majority develop little or no refractive error and are emmetropic. The causes of refractive error, especially myopia, have been the subject of debate for more than a century. Some have held that myopia is primarily an inherited disorder, and others, that myopia is caused by protracted near work and, especially, by accommodation during protracted near work. It has not been possible, based solely on clinical observations, to resolve the relative roles of heredity versus environment in the development of refractive error. In the mid-1970s, several animal models were developed to study the mechanisms underlying refractive error. Using animal models, it was found that the visual environment exerts a powerful influence on refractive state by controlling the axial length of the eye during the postnatal developmental period. Although several species have been examined, three have emerged as primary models and have played complementary roles: tree shrews (mammals closely related to primates), chicks, and monkeys. Each has advantages and disadvantages. Collectively, research on animal models has provided evidence on three issues, namely that (1) the visual environment can produce refractive error; (2) an emmetropization mechanism normally guides eyes to low refractive error; and (3) under-accommodation, rather than excessive accommodation, may cause myopia. Two decades of research on animal models have provided criteria that may be used to evaluate the usefulness of additional species as models of emmetropization.

[1]  Young Fa The nature and control of myopia. , 1977 .

[2]  J. Wallman,et al.  Visual influences on diurnal rhythms in ocular length and choroidal thickness in chick eyes. , 1998, Experimental eye research.

[3]  J. Wallman,et al.  Developmental aspects of experimental myopia in chicks: Susceptibility, recovery and relation to emmetropization , 1987, Vision Research.

[4]  T T Norton,et al.  Effect of interrupted lens wear on compensation for a minus lens in tree shrews. , 1999, Optometry and vision science : official publication of the American Academy of Optometry.

[5]  P. Hung,et al.  Study of myopia among aboriginal school children in Taiwan , 1988, Acta ophthalmologica. Supplement.

[6]  F. Schaeffel,et al.  6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia , 1994, Vision Research.

[7]  H. Jensen Myopia progression in young school children. A prospective study of myopia progression and the effect of a trial with bifocal lenses and beta blocker eye drops. , 1991, Acta ophthalmologica. Supplement.

[8]  C. S. Lam,et al.  The incidence of refractive errors among school children in Hong Kong and its relationship with the optical components , 1991 .

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

[10]  G. V. Alphen On emmetropia and ametropia. , 1961 .

[11]  C. Wildsoet,et al.  Active emmetropization--evidence for its existence and ramifications for clinical practice. , 1997, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

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

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

[14]  P. Hendrickson,et al.  Accommodation demand and deprivation in kitten ocular development. , 1985, Investigative ophthalmology & visual science.

[15]  E. Irving,et al.  Inducing ametropias in hatchling chicks by defocus—Aperture effects and cylindrical lenses , 1995, Vision Research.

[16]  H R Taylor,et al.  Prevalence of myopia in adults: implications for refractive surgeons. , 1997, Journal of refractive surgery.

[17]  J. Sivak,et al.  Experimentally induced myopia in chicks: Morphometric and biochemical analysis during the first 14 days after hatching , 1988, Vision Research.

[18]  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 : official publication of the American Academy of Optometry.

[19]  R. Held,et al.  Myopic children show insufficient accommodative response to blur. , 1993, Investigative ophthalmology & visual science.

[20]  Mark B. Friedman,et al.  Simple devices for restricting the visual fields of birds , 1978 .

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

[22]  G. Bock,et al.  Myopia and the control of eye growth , 1990 .

[23]  R. Held,et al.  A dynamic relationship between myopia and blur-driven accommodation in school-aged children , 1995, Vision Research.

[24]  N. Mcbrien,et al.  The effects of blockade of retinal cell action potentials on ocular growth, emmetropization and form deprivation myopia in young chicks , 1995, Vision Research.

[25]  S STENSTROM,et al.  Investigation of the variation and the correlation of the optical elements of human eyes. , 1948, American journal of optometry and archives of American Academy of Optometry.

[26]  R D Sperduto,et al.  Prevalence of myopia in the United States. , 1983, Archives of ophthalmology.

[27]  J. Davey,et al.  Emmetropia and its aberrations; a study in the correlation of the optical components of the eye. , 1957, Special report series (Medical Research Council (Great Britain)).

[28]  H. Howland,et al.  Differences in eye growth and the response to visual deprivation in different strains of chicken , 1995, Vision Research.

[29]  J. Wallman,et al.  Local retinal regions control local eye growth and myopia. , 1987, Science.

[30]  F. Schaeffel,et al.  Mathematical model of emmetropization in the chicken. , 1988, Journal of the Optical Society of America. A, Optics and image science.

[31]  M. Tigges,et al.  Emmetropization in the rhesus monkey (Macaca mulatta): birth to young adulthood. , 1999, Investigative ophthalmology & visual science.

[32]  W. Hodos,et al.  Experimental myopia in chicks: ocular refraction by electroretinography. , 1985, Investigative ophthalmology & visual science.

[33]  J. Wallman,et al.  Visual deprivation causes myopia in chicks with optic nerve section. , 1987, Current eye research.

[34]  D I Flitcroft,et al.  The lens paradigm in experimental myopia: oculomotor, optical and neurophysiological considerations , 1999, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[35]  N. Mcbrien,et al.  Experimental myopia in a diurnal mammal (Sciurus carolinensis) with no accommodative ability. , 1993, The Journal of physiology.

[36]  J. Wallman,et al.  Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid. , 1997, Current eye research.

[37]  K. Zadnik,et al.  The utility of three predictors of childhood myopia: a Bayesian analysis , 1995, Vision Research.

[38]  J. Lebensohn The Causes and Prevention of Acquired Myopia , 1958 .

[39]  A. Steiger Die Entstehung der sphärischen Refraktionen des menschlichen Auges : Übersichtigkeit, Normalsichtigkeit, Kurzsichtigkeit , 1913 .

[40]  Howard C. Howland,et al.  Natural accommodation in the growing chicken , 1986, Vision Research.

[41]  W. Stell,et al.  Basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) act as stop and go signals to modulate postnatal ocular growth in the chick. , 1994, Experimental eye research.

[42]  Chien-Jen Chen,et al.  Nation‐wide survey of myopia among schoolchildren in Taiwan, 1986 , 1988, Acta ophthalmologica. Supplement.

[43]  J. Wallman,et al.  Local ocular compensation for imposed local refractive error , 1990, Vision Research.

[44]  J. Woodhouse,et al.  Emmetropisation in human infancy: Rate of change is related to initial refractive error , 1995, Vision Research.

[45]  C. P. Hughes,et al.  Observations on the afferent and efferent connections of the avian isthmo-optic nucleus , 1978, Brain Research.

[46]  Earl L. Smith,et al.  Effects of optically induced blur on the refractive status of young monkeys , 1994, Vision Research.

[47]  M. R. Bryant,et al.  Optical feedback controlled scleral remodeling as a mechanism for myopic eye growth. , 1998, Journal of theoretical biology.

[48]  J. Pettigrew,et al.  Experimental myopia and anamalous eye growth patterns unaffected by optic nerve section in chickens: Evidence for local control of eye growth , 1988 .

[49]  F. Billson,et al.  Monocular axial myopia associated with neonatal eyelid closure in human infants. , 1981, American journal of ophthalmology.

[50]  J. Siegwart,et al.  Regulation of the mechanical properties of tree shrew sclera by the visual environment , 1999, Vision Research.

[51]  G. L. Walls,et al.  The Vertebrate Eye and Its Adaptive Radiation. , 2013 .

[52]  J. Hassell,et al.  Increased aggrecan (cartilage proteoglycan) production in the sclera of myopic chicks. , 1991, Developmental biology.

[53]  A J Adams,et al.  Myopia. The nature versus nurture debate goes on. , 1996, Investigative ophthalmology & visual science.

[54]  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.

[55]  J. Wallman,et al.  The eyes of young chickens grow toward emmetropia. , 1981, Investigative ophthalmology & visual science.

[56]  J. Wallman,et al.  Evidence that increased scleral growth underlies visual deprivation myopia in chicks. , 1991, Investigative ophthalmology & visual science.

[57]  K. Zadnik Myopia Development in Childhood , 1997 .

[58]  H. Fledelius OPHTHALMIC CHANGES FROM AGE OF 10 TO 18 YEARS , 1980, Acta ophthalmologica.

[59]  W S Oetting,et al.  A second locus for familial high myopia maps to chromosome 12q. , 1998, American journal of human genetics.

[60]  J K Lauber,et al.  Influence of Miotics, Diamox and Vision Occluders on Light-Induced Buphthalmos in Domestic Fowl.∗ , 1965, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

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

[62]  E S Avetisov,et al.  A study of biochemical and biomechanical qualities of normal and myopic eye sclera in humans of different age groups. , 1983, Metabolic, pediatric, and systemic ophthalmology.

[63]  A. Sorsby,et al.  A longitudinal study of refraction and its components during growth. , 1969, Special report series (Medical Research Council (Great Britain)).

[64]  H. Fledelius OPHTHALMIC CHANGES FROM AGE OF 10 TO 18 YEARS , 1982, Acta ophthalmologica.

[65]  A. W. Kirby,et al.  Elongation of cat eyes following neonatal lid suture. , 1982, Investigative ophthalmology & visual science.

[66]  Goss Da,et al.  Selected review on genetic factors in myopia. , 1988 .

[67]  Neville A. McBrien,et al.  Normal development of refractive state and ocular component dimensions in the tree shrew (Tupaia belangeri) , 1992, Vision Research.

[68]  J. E. Cronin,et al.  Comparative Biology and Evolutionary Relationships of Tree Shrews , 1981, Advances in Primatology.

[69]  A SORSBY,et al.  Refraction and its components during the growth of the eye from the age of three. , 1962, Medical Research Council memorandum.

[70]  E. Irving,et al.  Inducing Myopia, Hyperopia, and Astigmatism in Chicks , 1991, Optometry and vision science : official publication of the American Academy of Optometry.

[71]  E. Dunphy,et al.  Myopia among American male graduate students. , 1968, American journal of ophthalmology.

[72]  N. Mcbrien,et al.  A REVIEW AND EVALUATION OF THEORIES OF REFRACTIVE ERROR DEVELOPMENT , 1984, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[73]  Lynn Marran,et al.  Moving the retina: Choroidal modulation of refractive state , 1995, Vision Research.

[74]  E. Smith,et al.  Axial lengths and refractive errors in kittens reared with an optically induced anisometropia. , 1980, Investigative ophthalmology & visual science.

[75]  P. Kiely,et al.  Effects of retinal image degradation on ocular growth in cats. , 1984, Investigative ophthalmology & visual science.

[76]  Adrian Glasser,et al.  Accommodation, refractive error and eye growth in chickens , 1988, Vision Research.

[77]  Earl L. Smith,et al.  Extended-Wear, Soft, Contact Lenses Produce Hyperopia in Young Monkeys , 1996, Optometry and vision science : official publication of the American Academy of Optometry.

[78]  Frank Schaeffel,et al.  A simple mechanism for emmetropization without cues from accommodation or colour , 1994, Vision Research.

[79]  F. A. Young The effect of restricted visual space on the primate eye. , 1961, American journal of ophthalmology.

[80]  J. Rada,et al.  Reduced extracellular matrix in mammalian sclera with induced myopia , 1995, Vision Research.

[81]  S. Sherman,et al.  Loss of Y-cells in the lateral geniculate nucleus of monocularly deprived tree shrews. , 1977, Science.

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

[83]  V. Casagrande,et al.  Reduced lens development in lid-suture myopia. , 1978, Experimental eye research.

[84]  Joanne Katz,et al.  Epidemiology of myopia. , 2002, Epidemiologic Reviews.

[85]  L. Atwood,et al.  Evidence that a locus for familial high myopia maps to chromosome 18p. , 1998, American journal of human genetics.

[86]  B. Curtin The Myopias: Basic Science and Clinical Management , 1985 .

[87]  F. Schaeffel,et al.  Local Changes in Eye Growth induced by Imposed Local Refractive Error despite Active Accommodation , 1997, Vision Research.

[88]  R. Held,et al.  Effects of spectacle intervention on the progression of myopia in children. , 1999, Optometry and vision science : official publication of the American Academy of Optometry.

[89]  R. Held,et al.  Emmetropization and the progression of manifest refraction in children followed from infancy to puberty , 1993 .

[90]  J. Tigges,et al.  Postnatal axial eye elongation in normal and visually deprived rhesus monkeys. , 1990, Investigative ophthalmology & visual science.

[91]  Lim Mk,et al.  Myopia and educational attainment in 421,116 young Singaporean males. , 1992, Annals of the Academy of Medicine, Singapore.

[92]  W. Hodos,et al.  Thermal gradients in the chick eye: a contributing factor in experimental myopia. , 1987, Investigative ophthalmology & visual science.

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

[94]  F. Schaeffel,et al.  Flicker parameters are different for suppression of myopia and hyperopia , 1997, Vision Research.

[95]  T. T. Norton,et al.  Experimental myopia in tree shrews. , 2007, Ciba Foundation symposium.

[96]  D. Berson,et al.  The influence of study habits on myopia in Jewish teenagers. , 1993, Journal of pediatric ophthalmology and strabismus.

[97]  K. Zadnik,et al.  How applicable are animal myopia models to human juvenile onset myopia? , 1995, Vision Research.

[98]  D. Hubel,et al.  Plasticity of ocular dominance columns in monkey striate cortex. , 1977, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[99]  Earl L. Smith,et al.  Effects of chronic optical defocus on the kitten's refractive status , 1989, Vision Research.

[100]  L. Lin,et al.  Twin study on myopia. , 1987, Acta geneticae medicae et gemellologiae.

[101]  N. Mcbrien,et al.  Atropine reduces experimental myopia and eye enlargement via a nonaccommodative mechanism. , 1993, Investigative ophthalmology & visual science.

[102]  P. B. Donzis,et al.  Refractive development of the human eye. , 1985, Archives of ophthalmology.

[103]  E. STRÖMBERG,et al.  XXXIV: ÜBER REFRAKTION UND ACHSENLÄNGE DES MENSCHLICHEN AUGES , 1936 .

[104]  A. Laties,et al.  Muscarinic antagonist effects on experimental chick myopia. , 1991, Experimental eye research.

[105]  T T Norton,et al.  Animal models of emmetropization: matching axial length to the focal plane. , 1995, Journal of the American Optometric Association.

[106]  F. W. Weymouth,et al.  Notes on ametropia; a further analysis of Stenstrom's data. , 1947, American journal of optometry and archives of American Academy of Optometry.

[107]  A J Adams,et al.  The effect of parental history of myopia on children's eye size. , 1994, JAMA.

[108]  H. Fledelius,et al.  Reappraisal of the human ocular growth curve in fetal life, infancy, and early childhood. , 1996, The British journal of ophthalmology.

[109]  N. Mcbrien,et al.  Lid-suture myopia in tree shrews with retinal ganglion cell blockade , 1994, Visual Neuroscience.

[110]  D. Troilo Neonatal eye growth and emmetropisation—A literature review , 1992, Eye.

[111]  R. Cook,et al.  Refractive and ocular findings in the newborn. , 1951, American journal of ophthalmology.

[112]  J. Angle,et al.  The epidemiology of myopia. , 1980, American journal of epidemiology.

[113]  R. Malach,et al.  Emmetropization: a vision-dependent phenomenon. , 1981, Investigative ophthalmology & visual science.

[114]  B J Curtin,et al.  Normal and staphylomatous sclera of high myopia. An electron microscopic study. , 1979, Archives of ophthalmology.

[115]  T. Wiesel,et al.  Neural control of eye growth and experimental myopia in primates. , 2007, Ciba Foundation symposium.

[116]  F. Blodi Eugene Wolff's Anatomy of the Eye and Orbit , 1977 .

[117]  Francis Heed Adler,et al.  Adler's Physiology of the eye;: Clinical application , 1976 .

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

[119]  K. Schmid,et al.  Sharp vision: a prerequisite for compensation to myopic defocus in the chick? , 1998, Current eye research.

[120]  J. Mcneely,et al.  Mammals of Thailand. , 1977 .

[121]  W Hodos,et al.  Retinal-image degradation produces ocular enlargement in chicks. , 1984, Investigative ophthalmology & visual science.

[122]  S. Sherman,et al.  Differential effects of early monocular deprivation on binocular and monocular segments of cat striate cortex. , 1977, Journal of neurophysiology.

[123]  T N Wiesel,et al.  Effect of dark-rearing on experimental myopia in monkeys. , 1978, Investigative ophthalmology & visual science.

[124]  K J Saunders,et al.  Early refractive development in humans. , 1995, Survey of ophthalmology.

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

[126]  W. L. Weller,et al.  How thick should a retina be? A comparative study of mammalian species with and without intraretinal vasculature , 1991, Vision Research.

[127]  N. Mcbrien,et al.  Form deprivation myopia: elastic properties of sclera. , 1995, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[128]  R. W. Rodieck The vertebrate retina : principles of structure and function , 1973 .

[129]  L. Cyert,et al.  Baseline Characteristics in the Myopia Progression Study, a Clinical Trial of Bifocals to Slow Myopia Progression , 1998, Optometry and vision science : official publication of the American Academy of Optometry.

[130]  A SORSBY,et al.  Emmetropia and its aberrations. , 1956, Transactions. Ophthalmological Society of the United Kingdom.

[131]  F. Schaeffel,et al.  Constant light affects retinal dopamine levels and blocks deprivation myopia but not lens-induced refractive errors in chickens , 1994, Visual Neuroscience.

[132]  D. Nickla,et al.  Scleral changes in chicks with form-deprivation myopia. , 1990, Current eye research.

[133]  The optical effects of eyelid closure on the eyes of kittens reared in light and dark. , 1984, Current eye research.

[134]  N. Mcbrien,et al.  Form-deprivation myopia induces activation of scleral matrix metalloproteinase-2 in tree shrew. , 1996, Investigative ophthalmology & visual science.

[135]  M. J. Hirsch The relationship between refractive state of the eye and intelligence test scores. , 1959, American journal of optometry and archives of American Academy of Optometry.

[136]  J. Lebensohn Refraction and Its Components in Twins , 1963 .

[137]  H. Howland,et al.  The mechanism of corneal accommodation in chicks , 1994, Vision Research.

[138]  E. Smith,et al.  Developmental visual system anomalies and the limits of emmetropization. , 1999, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[139]  T. T. Norton,et al.  The susceptible period for deprivation-induced myopia in tree shrew , 1998, Vision Research.

[140]  K. Schmid,et al.  Effects on the compensatory responses to positive and negative lenses of intermittent lens wear and ciliary nerve section in chicks , 1996, Vision Research.

[141]  J. Wallman,et al.  Growth of the two layers of the chick sclera is modulated reciprocally by visual conditions. , 1997, Investigative ophthalmology & visual science.