Alexander H. Ward

The wavelength composition and temporal modulation of ambient lighting strongly affect refractive development in young tree shrews

Abstract 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 ± 0.01 mm 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 cue for postnatal refractive development, and that short‐wavelength temporal flicker provides an important cue for assessing and signaling defocus. Graphical abstract Figure. No Caption available. HighlightsExamined effect of long and short wavelengths on refractive development.Studied tree shrews, cone‐dominated dichromatic mammals closely related to primates.Narrow‐band red light (626 nm) slowed vitreous chamber growth, producing hyperopia.Flickering narrow‐band blue light (464 nm) produced elongated vitreous and myopia.Wavelength exposure in young tree shrews has powerful effects on emmetropization.

Long-wavelength (red) light produces hyperopia in juvenile and adolescent tree shrews.

&NA; 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 &mgr;m vs. normal 57 ± 3 &mgr;m (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. Graphical abstract Figure. No caption available. HighlightsJuvenile and adolescent tree shrews become hyperopic in narrow‐band red light.The vitreous chamber is smaller than normal and the choroid is thicker.Tree shrews at these ages do not become hyperopic in response to a plus lens.The continuing response to red contrasts with the lack of response to a plus lens.The emmetropization mechanism can slow eye growth in juvenile and adolescent animals.

Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews

We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.