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.

Shortly after birth, the eyes of most animals (including humans) are hyperopic because the short axial length places the retina in front of the focal plane. During postnatal development, an emmetropization mechanism uses cues related to refractive error to modulate the growth of the eye, moving the retina toward the focal plane. One possible cue may be longitudinal chromatic aberration (LCA), to signal if eyes are getting too long (long [red] wavelengths in better focus than short [blue]) or too short (short wavelengths in better focus). It could be difficult for the short-wavelength sensitive (SWS, “blue”) cones, which are scarce and widely spaced across the retina, to detect and signal defocus of short wavelengths. We hypothesized that the SWS cone retinal pathway could instead utilize temporal (flicker) information. We thus tested if exposure solely to long-wavelength light would cause developing eyes to slow their axial growth and remain refractively hyperopic, and if flickering short-wavelength light would cause eyes to accelerate their axial growth and become myopic. Four groups of infant northern tree shrews (Tupaia glis belangeri, dichromatic mammals closely related to primates) began 13 days of wavelength treatment starting at 11 days of visual experience (DVE). Ambient lighting was provided by an array of either long-wavelength (red, 626±10 nm) or short-wavelength (blue, 464±10 nm) light-emitting diodes placed atop the cage. The lights were either steady, or flickering in a pseudo-random step pattern. The approximate mean illuminance (in human lux) on the cage floor was red (steady, 527 lux; flickering, 329 lux), and blue (steady, 601 lux; flickering, 252 lux). Refractive state and ocular component dimensions were measured and compared with a group of age-matched normal animals (n=15 for refraction (first and last days); 7 for ocular components) raised in broad spectrum white fluorescent colony lighting (100-300 lux). During the 13 day period, the refraction of the normal animals decreased from (mean±SEM) 5.8±0.7 diopters (D) to 1.5±0.2 D as their vitreous chamber depth increased from 2.77±0.01mm to 2.80±0.03 mm. Animals exposed to red light (both steady and flickering) remained hyperopic throughout the treatment period so that the eyes at the end of wavelength treatment were significantly hyperopic (7.0±0.7 D, steady; 4.7±0.8 D, flickering) compared with the normal animals (p<0.01). The vitreous chamber of the steady red group (2.65±0.03 mm) was significantly shorter than normal (p<0.01). On average, steady blue light had little effect; the refractions paralleled the normal refractive decrease. In contrast, animals housed in flickering blue light increased the rate of refractive decrease so that the eyes became significantly myopic (−2.9±1.3 D) compared with the normal eyes and had longer vitreous chambers (2.93±0.04 mm). Upon return to colony lighting, refractions in all groups gradually returned toward emmetropia. These data are consistent both with the hypothesis that LCA can be an important visual...

The responses of adjacent neurons in inferior temporal (IT) cortex carry signals that are to a large degree independent (Gawne and Richmond, 1993). Adjacent primary visual cortical neurons have similar orientation tuning (Hubel and Wiesel, 1962, 1968), suggesting that their responses might be more redundant than those in IT. We recorded the responses of 26 pairs of adjacent complex cells in the primary visual cortex of two awake monkeys while using both a set of 16 bar-like stimuli, and a more complex set of 128 two-dimensional patterns. Linear regression showed that 40% of the signal variance of one neuron was related to that of the other when the responses to the bar-like stimuli were considered. However, when the responses to the two-dimensional stimuli were included in the analysis, only 19% of the signal variance of one neuron was related to that of the adjacent one, almost exactly the same results as found in IT. An information theoretic analysis gave similar results. We hypothesize that this trend toward independence of information processing by adjacent cortical neurons is a general organizational strategy used to maximize the amount of information carried in local groups.

Recent magnetic resonance spectroscopy (MRS) studies suggest that abnormalities of the glutamatergic system in schizophrenia may be dependent on illness stage, medication status, and symptomatology. Glutamatergic metabolites appear to be elevated in the prodromal and early stages of schizophrenia but unchanged or reduced below normal in chronic, medicated patients. However, few of these studies have measured metabolites with high-field 7T MR scanners, which offer higher signal-to-noise ratio and better spectral resolution than 3T scanners and facilitate separation of glutamate and glutamine into distinct signals. In this study, we examined glutamate and other metabolites in the dorsal anterior cingulate cortex (ACC) of first-episode schizophrenia patients. Glutamate and N-acetylaspartate (NAA) were significantly lower in schizophrenia patients vs controls. No differences were observed in levels of glutamine, GABA, or other metabolites. In schizophrenia patients but not controls, GABA was negatively correlated with the total score on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as well as the immediate memory and language subscales. Our findings suggest that glutamate and NAA reductions in the ACC may be present early in the illness, but additional large-scale studies are needed to confirm these results as well as longitudinal studies to determine the effect of illness progression and treatment. The correlation between GABA and cognitive function suggests that MRS may be an important technique for investigating the neurobiology underlying cognitive deficits in schizophrenia.

In infant tree shrews, exposure to narrow-band long-wavelength (red) light, that stimulates long-wavelength sensitive cones almost exclusively, slows axial elongation and produces hyperopia. We asked if red light produces hyperopia in juvenile and adolescent animals, ages when plus lenses are ineffective. Animals were raised in fluorescent colony lighting (100–300 lux) until they began 13 days of red-light treatment at 11 (n=5, “infant”), 35 (n=5, “juvenile”) or 95 (n=5, “adolescent”) days of visual experience (DVE). LEDs provided 527–749 lux on the cage floor. To control for the higher red illuminance, a fluorescent control group (n=5) of juvenile (35 DVE) animals was exposed to ~ 975 lux. Refractions were measured daily; ocular component dimensions at the start and end of treatment and end of recovery in colony lighting. These groups were compared with normals (n=7). In red light, the refractive state of both juvenile and adolescent animals became significantly (P<0.05) hyperopic: juvenile 3.9±1.0 diopters (D, mean±SEM) vs. normal 0.8±0.1 D; adolescent 1.6±0.2 D vs. normal 0.4±0.1 D. The fluorescent control group refractions (0.6±0.3 D) were normal. In red-treated juveniles the vitreous chamber was significantly smaller than normal (P<0.05): juvenile 2.67±0.03 mm vs. normal 2.75±0.02 mm. The choroid was also significantly thicker: juvenile 77±4 μm vs. normal 57±3 μm (P<0.05). Although plus lenses do not restrain eye growth in juvenile tree shrews, the red light-induced slowed growth and hyperopia in juvenile and adolescent tree shrews demonstrates that the emmetropization mechanism is still capable of restraining eye growth at these ages.