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In post-natal developing eyes a feedback mechanism uses optical cues to regulate axial growth so as to achieve good focus, a process termed emmetropization. However, the optical cues that the feedback mechanism uses have remained unclear. Here we present evidence that a primary visual cue may be the detection of different image statistics by the short-wavelength sensitive (SWS) and long-wavelength sensitive (LWS) cone photoreceptors, caused by longitudinal chromatic aberration (LCA). We use as a model system the northern tree shrew Tupaia belangeri, diurnal cone-dominated dichromatic mammals closely related to primates. We present an optical model in which the SWS and LWS photoreceptors each represent an image at different levels of defocus and different spectral lighting conditions. The model posits that an imbalance between SWS and LWS image statistics directs eye growth towards the point at which these image statistics are in balance. Under spectrally broadband (“white”) lighting, the focus of the eye is driven to a target point approximately in the middle of the visible spectrum, which is emmetropia. Calculations suggest that the SWS cone array, despite the sparse number of SWS cones, can plausibly detect the wavelength-dependent differences in defocus and guide refractive development. The model is consistent with the effects of various narrow-band illuminants on emmetropization in tree shrews. Simulations suggest that common artificial light spectra do not interfere with emmetropization. Simulations also suggest that multi-spectral multi-focal lenses, where the different optical zones of a multifocal lens have different spectral filtering properties, could be an anti-myopia intervention.

We examined gene expression in tree shrew choroid in response to three different myopiagenic conditions: minus lens (ML) wear, form deprivation (FD), and continuous darkness (DK). Four groups of tree shrews (n = 7 per group) were used. Starting 24 days after normal eye opening (days of visual experience [DVE]), the ML group wore a monocular −5 D lens for 2 days. The FD group wore a monocular translucent diffuser for 2 days. The DK group experienced continuous darkness binocularly for 11 days, starting at 17 DVE. An age-matched normal group was examined at 26 DVE. Quantitative PCR was used to measure the relative (treated eye vs. control eye) differences in mRNA levels in the choroid for 77 candidate genes. Small myopic changes were observed in the treated eyes (relative to the control eyes) of the ML group (−1.0 ± 0.2 D; mean ± SEM) and FD group (−1.9 ± 0.2 D). A larger myopia developed in the DK group (−4.4 ± 1.0 D) relative to Normal eyes (both groups, mean of right and left eyes). In the ML group, 28 genes showed significant differential mRNA expression; eighteen were down-regulated. A very similar pattern occurred in the FD group; twenty-seven of the same genes were similarly regulated, along with five additional genes. Fewer expression differences in the DK group were significant compared to normal or the control eyes of the ML and FD groups, but the pattern was similar to that of the ML and FD differential expression patterns. These data suggest that, at the level of the choroid, the gene expression signatures produced by “GO” emmetropization signals are highly similar despite the different visual conditions.

To examine the susceptible period for deprivation-induced myopia, six groups of tree shrew pups (Tupaia glis belangeri) were monocularly deprived for 12 days with an opaque occluder starting 7, 15, 21, 33, 48, or 63 days after natural eyelid opening. Compared to the untreated fellow control eye, significant myopia and vitreous chamber elongation were produced by the deprivation in all six groups. The effect was greater in the middle three groups in comparison with the youngest and the two oldest groups and the amount of induced myopia and axial elongation was not proportional to the normal rate of axial growth. The peak period of susceptibility was between approximately 15 and 45 days after eye opening during the juvenile, slow-elongation phase of ocular development when the eye is within 7% of its adult axial length. Significant myopia and axial elongation were also induced in adult animals by 70 days of monocular deprivation. To examine recovery from deprivation–induced myopia, the occluder was removed at the end of the 12 day deprivation period. After an additional 48 days of binocular visual experience, no significant myopia was present in the previously deprived eyes in any experimental group. During the recovery period, the elongation rate of the previously deprived eyes was reduced in comparison with the control eyes while normal corneal flattening and lens development continued, thus reducing the myopia. No difference in corneal curvature, relative to the untreated control eyes, was found after deprivation or after the recovery period. Data are presented which suggests that changes in the thickness of the choroid may occur in this mammal during deprivation and recovery that are in the same direction, but of smaller magnitude, than those reported in the chicken. The results of this study provide evidence that visually guided emmetropization occurs in this mammalian species during a period of ocular development analogous to the juvenile period in humans.

Investigations into the plasticity of eye growth and refractive error development have significantly expanded our knowledge of animal models of myopia in the last 15 yr. The applicability of this information is as yet undetermined, but hopefully this information will be useful in learning more about human myopia. This paper presents a critical review of the animal myopia literature as those data relate to the human condition. Differences between the chicken, tree shrew, and primate animal models of myopia are outlined, and the various experimental paradigms used to investigate refractive error development and ocular growth in the chicken are compared. Specific arguments against the application of animal models of myopia to the etiology of human juvenile onset myopia include the following: (1) there is no deprivation of form vision in the environment of the school-aged child as severe as that required to induce myopia in animals; (2) the sensitive period for deprivation myopia in animals appears to be too early to account for human juvenile onset myopia; and (3) studies in the chicken using spectacle lenses to create dioptric blur involve a choroidal thickness modulation that has no human analog. Ultimately, the results of investigations into the cellular and biochemical modulation of eye growth in animals may be the most relevant to human myopia.

Temporal modulation sensitivity functions (MSFs) were measured behaviorally in three adult tree shrews (Tupaia belangeri). Shrews were trained to detect temporal sinusoidally-modulated full-field luminance variations in one of three stimuli, the two alternatives being static stimuli of equal size and time-averaged luminance (34 cd/m2). Modulation depth was varied trial-by-trial using a modified staircase technique under ambient illumination of 16 lux. Threshold modulation depths were determined for five temporal frequencies ranging from 3.7 to 47 Hz. Results revealed temporal MSFs that peaked at 15 Hz with a low-frequency roll-off and an extrapolated high-frequency cut-off beyond 50 Hz. These findings confirm the comparatively good temporal vision of Tupaia predicted by behavioral observations.

The normal development of refractive state, ocular components and simple visually-guided behaviors was examined in maternally-reared tree shrews. Six groups consisting of 5 animals each were anesthetized and examined after 0, 15, 30, 45, 60 and 75 days of normal binocular visual exposure. Measures in the 75-day group provided values for an unproved schematic eye of the tree shrew. Cycloplegic refraction showed a marked hyperopia (+25 D) at eye opening which decreased rapidly during the first 15 days of visual exposure and stabilized near the value (+5 D) expected in an eye of this axial length (approx. 7.8 mm). Corneal radius increased slightly during development. Anterior segment depth, measured by A-scan ultrasonography, seemed to complete most of its development at an earlier age (15–30 days of visual exposure) than did other ocular parameters. Lens thickness increased steadily throughout development. Vitreous chamber depth increased rapidly until 15 days of visual exposure, and then decreased because the lens thickness increased more rapidly than axial length. Crude orienting to, and following of, large objects developed shortly after eye opening (median age at onset, 5 and 6 days, respectively). Triggered visual placing responses developed at about the same time that the refractive state completed the rapid drop from highly hyperopic values. The slowed rate of ocular development after 15 days of visual exposure may be related to increased retinal activity that is permitted by neural maturation and by the presence of a relatively well-focussed retinal image. The increased activity may influence the final dimensions of the eye to coordinate the axial length with the focal length of the eye.

The retina of the tree shrew (Tupaia belangeri) is heavily cone dominated, rods comprising less than 4% of the total photoreceptors. Spectral mechanisms and color vision were investigated in this species in both behavioral and electrophysiological experiments. In confirmation of an earlier investigation, the tree shrew was found to have a clear spectral neutral point (at ca 505 nm) and is thus a dichromat. Spectral sensitivity functions determined in an increment threshold discrimination task show two clear peaks (at ca 440 and 550-560 nm) with an intermediate region of lowered sensitivity centered at about 500 nm. Spectral sensitivity of the two cone types in this animal were determined using ERG flicker photometry. One of these cone classes has a peak at 556 nm; the other has a 444 nm peak.

To study the correlation between blood–retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (Pin) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P

The response to short duration light stimuli of single optic tract fibres from on-center retinal ganglion cells was measured. Seven kinds of response measures were compared. Some of these, i.e. the detectability indices, involve the mean response level and the variability of the response as well. The involvement of the variability, although noticeable on the threshold level, did not appreciably change the shape of the increment threshold curves. The different statistical properties of the response of sustained cells as compared to transient cells were not revealed in the increment threshold curves either. It is concluded that the choice of the response measure is not critical and may be made on considering the compatibility of electrophysiological data to psychophysical data.