David Troilo

Visual deprivation causes myopia in chicks with optic nerve section

Deprivation of form vision restricted to a region of the retina produces myopia and axial elongation only in that region. We asked whether this control of eye growth by the presence or absence of visual stimuli might take place entirely within the eye. Chicks with neonatal optic nerve section, wearing an occluder that deprived one half of the retina of form vision, had vitreous chamber elongation and myopia both restricted to the deprived region. Chicks with optic nerve section but without occluders had eyes smaller than normal with severe hyperopia. These results suggest that two different mechanisms may control eye growth, one within the eye and the other in the brain.

The regulation of eye growth and refractive state: An experimental study of emmetropization

During growth the vertebrate eye achieves a close match between the power of its optics and its axial length with the result that images are focused on the retina without accommodative effort (emmetropia). The possibility that vision is required for the regulation of eye growth was studied experimentally in chicks made myopic or hyperopic by different visual manipulations. After discontinuing these visual manipulations, the eyes returned quickly to emmetropia mainly by adjusting the growth of their vitreous chambers; growth stopped in eyes recovering from myopia and continued in eyes recovering from hyperopia. Because both hyperopic and myopic eyes were already larger than normal controls, the difference in growth indicates that refractive error, rather than eye size per se, guides the eye toward emmetropia. Evidence is also presented for nonvisual shape-related control of eye growth, but this is slow-acting and cannot explain the emmetropization from induced refractive errors. Both the visually guided and shape-related mechanisms work even in eyes with the optic nerve cut, indicating that the two mechanisms are local to the eye. Although the optic-nerve-sectioned eye can sense the sign of a refractive error and initially adjust growth accordingly, it eventually overshoots emmetropia and reverses the sign of the initial refractive error. Whether this is due to loss of feedback from the central nervous system or retinal ganglion cells is unclear.

Developing eyes that lack accommodation grow to compensate for imposed defocus.

The eyes of growing chicks adjust to correct for myopia (eye relatively long for the focal length of its optics) or hyperopia (eye relatively short for the focal length of its optics). Eyes made functionally hyperopic with negative spectacle lenses become myopic and long, whereas eyes made functionally myopic with positive spectacle lenses become hyperopic and short. We report here that these compensatory growth adjustments occur not only in normal eyes but also in eyes unable to accommodate (focus) because of lesions to the Edinger-Westphal nuclei. Thus, at least in chicks, accommodation is not necessary for growth that reduces refractive errors during development, and may not be necessary for the normal control of eye growth.

Ocular development and visual deprivation myopia in the common marmoset (Callithrix jacchus)

The normal postnatal ocular development of the common marmoset (Callithrix jacchus) and the effects of visual deprivation on eye growth and refractive state are described. The marmoset normally undergoes a developmental process of emmetropization from high hyperopia at birth. This emmetropization is easily disrupted by visual deprivation produced by lid-suture. Myopia and axial elongation of the vitreous chamber are induced by visual deprivations of 12, 5, and 3 weeks duration. The development of axial myopia after 3 weeks of visual deprivation differs from longer duration deprivations in that the experimental eyes are initially shorter than normal and hyperopic at the end of the visual deprivation period, but subsequently become longer than normal and myopic. Visual deprivation myopia in the marmoset persists even after the deprivation is discontinued and a visual signal is restored. In all experimental groups, the development of the eye in response to the cessation of visual deprivation shows no slowing of vitreous chamber enlargement; the axial enlargement relative to the control eye is either maintained or increases and produces significantly greater myopia. These results suggest that the visual control of postnatal eye growth in the marmoset may be unidirectional in its response to visual experience and able only to increase the growth rate of the vitreous chamber, possibly after an initial delay.

Visual optics and retinal cone topography in the common marmoset (Callithrix jacchus)

The common marmoset (Callithrix jacchus) is a small, diurnal, New World monkey amenable to vision research. In this paper we describe the visual optics and cone photoreceptor topography of the normal adult marmoset. Paraxial optical ray-tracing shows that the marmoset eye is well represented as a scaled-down version of the human eye. The density of foveal and perifoveal cone photoreceptors in the marmoset is as high, and in peripheral retina higher, than those reported in humans and macaques. The foveal acuity predicted by the Nyquist limits set by the cone mosaic (30 c/deg) is in agreement with behavioral measures of visual acuity. Foveal depth of focus is remarkably small (< 0.2 D) for an eye of this size (axial length about 11 mm). Estimates of the amplitude of accommodation using infrared photorefraction indicate that the marmoset is capable of more than 20 D of accommodation.

Constant light produces severe corneal flattening and hyperopia in chickens

In this study we report on the effects of constant light (CL) on the refractive development and ocular morphology of White Leghorn chicks (Cornell K-strain). Refractive state and corneal curvature were measured by IR photoretinoscopy and IR keratometry respectively. The axial lengths of the ocular components were measured by A-scan ultrasonography. We find that constant light produces significant hyperopia compared to controls in as few as 10 days (7.4 vs 4.0 D). This is apparently the result of flatter than normal corneal curvature (radius of curvature: 3.22 vs 3.08 mm) as vitreous chamber depth is significantly deeper in CL eyes than controls at that age (5.6 vs 5.1 mm). In contrast to other reports, if CL rearing is continued for longer periods the hyperopia progresses, even though vitreous chamber depth continues to increase. After 11 weeks of CL severe hyperopia was observed (18.2 vs 2.8 D). Long term CL is also found to produce shallow anterior chambers, corneal thickening, lenticular thinning and cataracts, and damage to the retina, pigment epithelium, and choroid.

Neonatal eye growth and emmetropisation—A literature review

The refractive development of the neonatal eye has been the subject of much study and debate. In this paper the hypothetical mechanisms of emmetropisation and their relationship to the development of refractive errors will be reviewed. The evidence supporting visual feedback control of eye growth will be described, and the role of ocular accommodation will be discussed.

Characteristics of Accommodative Behavior During Sustained Reading in Emmetropes and Myopes

Accommodation has long been suspected to be involved in the development of myopia because near work, particularly reading, is known to be a risk factor. In this study, we measured several dynamic characteristics of accommodative behavior during extended periods of reading under close-to-natural conditions in 20 young emmetropic and stable myopic subjects. Accommodative responses, errors, and variability (including power spectrum analysis) were analyzed and related to accommodative demand and subject refractive error. All accommodative behaviors showed large inter-subject variability at all of the reading demands. Accommodative lags and variability significantly increased with closer demands for all subjects (ANOVA, p<0.05). Myopes had significantly greater variability in their accommodation responses compared to emmetropes (ANOVA, p<0.05) and had larger accommodative lags at further reading distances (unpaired t test p<0.05). Power spectrum analysis showed a significant increase in the power of accommodative microfluctuations with closer demands (ANOVA, p<0.05) and with increasing myopia at the closest reading demand (ANOVA, p<0.01). The difference in the stability of the accommodative behavior between individuals with different refractive states suggests a possible relationship between variability in accommodation and the development of myopia.

Differences in Eye Growth and the Response to Visual Deprivation in Different Strains of Chicken

Several laboratories studying visual deprivation myopia in the domestic chick report varying degrees of axial elongation and myopia induced by similar visual deprivation techniques. In this study we tested the hypothesis that in different strains of chick the eyes respond differently to visual deprivation. We compared under identical conditions two strains of White Leghorn chick commonly used in ocular development research--the Cornell-K strain (K) and Washington H & N Strain (H/N). The normal development of the eye was found to vary significantly between these strains of White Leghorn chicks. The K strain normally develops flatter corneas, thicker lenses, and larger eyes than the H/N strain. The response to visual deprivation also varies significantly between strains. For example, we find that 2 weeks of visual deprivation in the K strain results in less elongation of the vitreous chamber and flattening of the cornea yielding lower levels of induced myopia compared to the H/N strain. Our results show that while visual experience clearly affects normal ocular development in both strains of chick, the nature of the effect depends upon not only the type and duration of the experience but the genetics of the subject population as well.

Evaluation of AAV-Mediated Expression of Chop2-GFP in the Marmoset Retina

PURPOSE Converting inner retinal neurons to photosensitive cells by expressing channelrhodopsin-2 (ChR2) offers a novel approach for treating blindness caused by retinal degenerative diseases. In the present study, the recombinant adeno-associated virus serotype 2 (rAAV2)-mediated expression and function of a fusion construct of channelopsin-2 (Chop2) and green fluorescent protein (GFP) (Chop2-GFP) were evaluated in the inner retinal neurons in the common marmoset Callithrix jacchus. METHODS rAAV2 vectors carrying ubiquitous promoters were injected into the vitreous chamber. Expression of Chop2-GFP and functional properties of ChR2 were examined by immunocytochemical and electrophysiological methods 3 months after injection. RESULTS The percentage of Chop2-GFP-expressing cells in the ganglion cell layer was found to be retinal region- and animal age-dependent. The highest percentage was observed in the far-peripheral region. Chop2-GFP expression was also found in the foveal and parafoveal region. In the peripheral retina in young animals with high viral concentrations, the expression of Chop2-GFP was observed in all major classes of retinal neurons, including all major types of ganglion cells. The morphologic properties of Chop2-GFP-positive cells were normal for at least 3 months, and ChR2-mediated light responses were demonstrated by electrophysiological recordings. CONCLUSIONS The rAAV2-mediated expression of ChR2 was observed in the inner retinal neurons in the marmoset retina through intravitreal delivery. The marmoset could be a valuable nonhuman primate model for developing ChR2-based gene therapy for treating blinding retinal degenerative diseases.