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.

Keywords: Hyperopia; Longitudinal chromatic aberration; Myopia; Optical blur; Retinal signaling; Vitreous chamber.

Fig. 1

A. The temporal pattern of flickering light with superimposed large and small excursions (not to scale – see text). The pattern is pseudo-randomly generated and would repeat every 497 days if run continuously. B. Log magnitude of the Fourier transform of this temporal pattern indicating that a wide range of temporal frequencies were present in the flickering light arrays.

Fig. 2

The effect on refractive development in young tree shrews of steady and flickering, and red and blue, ambient light compared with fluorescent colony lighting. Positive numbers on the y-axis indicate hyperopic refractive error, and negative numbers, myopic refractive error. Thin lines show individual animals (mean of the two eyes.) Error bars are ± SEM. Dashed, black line indicates emmetropia (0 D refractive error). Black circles (“normal eyes”) are from the normal group raised exclusively in colony lighting. A: Refractions (n=5) during exposure to 13 days of steady red light (red, triangle symbols) followed by colony fluorescent lighting “recovery” (inverted white triangle symbols). All five animals became hyperopic compared to normals. When transferred to colony lighting, refractions returned toward normal levels. B: Flickering red light. Similar to A, all five animals became hyperopic and “recovered” in colony lighting. C: Exposure to steady blue light. One animal became myopic, another remained hyperopic, and the remaining three appeared to emmetropize normally. The overall pattern of refractive change during treatment was essentially normal. D: Exposure to flickering blue light. All seven animals became myopic relative to normals; two became highly myopic. Refractions returned toward normal after the animals were placed in colony lighting.

Fig. 3

A. Refractive state of the four wavelength-treated groups at the end of the 13-day treatment period. Values are the average of the right and left eyes, ± S.E.M. Age-matched normal refractions ± 95% confidence intervals are indicated by the solid and dashed horizontal black lines (n=15). Values significantly different from the age-matched normals are indicated by asterisks (Kruskal-Wallis with Dunn’s post-hoc test). Steady and flickering red light both produced strong hyperopia; steady blue light, on average, had no effect and flickering blue light was myopiagenic. B. End of wavelength treatment vitreous chamber depths. The most hyperopic group had the shortest vitreous chambers. Vitreous chamber depth was greater in groups with lower refractive state. Age-matched normal refractions ± 95% confidence intervals are indicated by the solid and dashed horizontal black lines (n=7).

Fig. 4

Association between change in refractive state and change in the depth of the vitreous chamber during the 13-day treatment period. Values are the average of the right and left eyes. Vitreous chamber depth changed in parallel with refractive change.