Homeostasis of Eye Growth and the Question of Myopia

An updated view on the role of dopamine in myopia

Evolution of eyes

The results of many studies in a variety of species have significantly advanced our understanding of the role of visual experience and the mechanisms of postnatal eye growth, and the development of myopia. This paper surveys and reviews the major contributions that experimental studies using animal models have made to our thinking about emmetropization and development of myopia. These studies established important concepts informing our knowledge of the visual regulation of eye growth and refractive development and have transformed treatment strategies for myopia. Several major findings have come from studies of experimental animal models. These include the eye's ability to detect the sign of retinal defocus and undergo compensatory growth, the local retinal control of eye growth, regulatory changes in choroidal thickness, and the identification of components in the biochemistry of eye growth leading to the characterization of signal cascades regulating eye growth and refractive state. Several of these findings provided the proofs of concepts that form the scientific basis of new and effective clinical treatments for controlling myopia progression in humans. Experimental animal models continue to provide new insights into the cellular and molecular mechanisms of eye growth control, including the identification of potential new targets for drug development and future treatments needed to stem the increasing prevalence of myopia and the vision-threatening conditions associated with this disease.

/pdf/imi-report-on-experimental-models-of-emmetropization-and-z72nyydfjb.pdf

IMI - Report on Experimental Models of Emmetropization and Myopia.

A paraxial schematic eye model for the growing C57BL/6 mouse.

The focal length of the vertebrate eye is a function of wavelength, i.e. the eye suffers from longitudinal chromatic aberration. Chromatic defocus is a particularly severe problem in eyes with high light-gathering ability, since depth of field is small due to a pupillary opening that is large in relation to the focal length of the eye. Calculations show that in such eyes only a narrow spectral band of light can be in focus on the retina. For the major part of the visual spectrum, spatial resolution should be limited by the optics of the eye and far lower than the resolving power achievable by the retinal cone photoreceptor mosaic. To solve this problem, fishes with irises unresponsive to light have developed lenses with multiple focal lengths. Well-focused images are created at the wavelengths of maximum absorbance of all spectral cone types. Multifocal lenses also appear to be present in some terrestrial species. In eyes with mobile irises, multifocal lenses are correlated with pupil shapes that allow all zones of the lens, with different refractive powers, to participate in the imaging process, irrespective of the state of pupil constriction.

/pdf/multifocal-lenses-compensate-for-chromatic-defocus-in-44l2u20zsf.pdf

Multifocal lenses compensate for chromatic defocus in vertebrate eyes.

By rearing fish in various monochromatic illuminations we investigated (1) the potential for compensation of refractive error due to chromatic aberration, (2) the contributions of the chromatic channels to emmetropization, and (3) the role of color cues in the control of eye growth. Cichlid fish (Aequidens pulcher) were reared for 6 months (12 h light/12 h dark) in monochromatic lights (623.5, 534.1, 485.0 nm; spectral purity 5–10 nm). Light levels were isoirradiant at 1.1·1012 quanta/s/cm2. Two control groups were reared in white light with down-welling illuminances of 0.2 and 33 lx. Nasotemporal diameters (NTDs) of the eyes were measured in relation to lens size. Due to the oblique axis of highest acuity vision in cichlids, NTD is considered to be a more important dimension than axial length. Variances in NTD were equally small in all rearing groups. NTDs were enlarged with increasing wavelengths of the rearing lights with highly significant values over controls in the red-light group. The wavelength-dependent size of the eyes matched the changes in focal length due to longitudinal chromatic aberration. Complete recovery from eye enlargement was observed after fish reared in red light were exposed to a white light regime for 5 weeks. Small variances in NTD in all groups indicated stringent control of eye growth in the absence of color cues. The reversibility of the increase in NTD in fish reared in red light suggests that the eyes were emmetropized by visually guided mechanisms. Eye size in fish reared in white light was intermediate between the values expected if only blue-sensitive single or the red- and green-sensitive double cones contributed to the control of eye growth. This suggests that all chromatic channels participate in emmetropizing the fish eye.

The eye of the blue acara (Aequidens pulcher, Cichlidae) grows to compensate for defocus due to chromatic aberration.

We investigated the suitability of fishes as animal models to study the involvement of the retinal dopaminergic system in the visually guided control of eye growth (emmetropization) Advantages of such a model system are (i) that all dopaminergic cells in the retina can be destroyed without apparent damage to other neurons, (ii) simple optical design and short depth of field of the eye, and (iii) continuous growth throughout life Depleting the retina of dopamine in Aequidens pulcher (Cichlidae) had no apparent effect on refractive state, since size and focal length of the eye were reduced by the same amount Furthermore, imposed defocus was compensated at a normal rate in spite of the absence of retinal dopamine In A pulcher, the dopaminergic system of the retina thus appears not to have an essential role in emmetropization Our results furthermore suggest that in eyes of more complicated optical design, manipulation of the retinal dopaminergic system may lead to unrelated effects indistinguishable from direct interference with emmetropization A major disadvantage of the fish model was that refractive state of the eye could not be measured accurately in vivo with standard methods

R. H. H. Kröger

Papers

Multifocal lenses compensate for chromatic defocus in vertebrate eyes.

The eye of the blue acara (Aequidens pulcher, Cichlidae) grows to compensate for defocus due to chromatic aberration.

Effects of retinal dopamine depletion on the growth of the fish eye.