The effects of light regimes and hormones on corneal growth in vivo and in organ culture

Abstract

Background When chicks are exposed to constant light during growth, their corneas become flatter and lighter in weight, and their anterior segments become shallower than those of chicks exposed to cyclical periods of light and dark. These effects have been correlated with constant light suppression of cyclical changes in melatonin levels. The question of whether light directly influences corneal growth (e.g. via cryptochromes in the cornea) or whether it acts remotely via the suppression of the melatonin rhythm has not yet been answered. Retinoic acid, an ubiquitous morphogen, also causes non-functional flattening during corneal growth, but its effect in vivo has not been correlated with light regimes. Purpose We wished to characterize and distinguish between hormonal and light effects on corneal growth. We used organ culture to study the direct effects of light regimes, melatonin, and retinoic acid, and compared these results with those of parallel in vivo experiments. Methodology In this study, eye drops containing melatonin or retinoic acid were applied to corneas exposed to constant light in vivo or in organ culture, and effects on corneal mass and hydration were measured. We applied a melatonin blocker, luzindole, to chick corneas in normal light/dark conditions to confirm that the observed melatonin effects are mediated at the cell membrane. Anterior chamber depth and refraction in vivo were measured. Principal Findings We found that, during constant light exposure, combined application of melatonin and retinoic acid eye drops increase the depth of the anterior segment in vivo, (p = 0.003) and interestingly, both also reduced the hyperopia of constant light exposure after two weeks (p = 0.002), thus partially reversing the effects of constant light. Retinoic acid increased corneal hydration in vivo (p = 0.030) but not in organ culture. Melatonin had no effect on corneal hydration in vivo, but in organ culture, melatonin significantly decreased hydration (p <0.001). Conclusions/Significance We found no evidence for a direct effect of light on corneal hydration in growing chick corneas in culture. Melatonin is required for normal corneal growth in vivo, and together melatonin and retinoic acid, or retinoic acid alone, affect the regulation of water content within the chick cornea. Melatonin also affects corneal hydration in vitro, but retinoic acid does not.

Myopes have significantly higher serum melatonin concentrations than non‐myopes

“…While our results show an association between refractive status and serum Mel, our data cannot be used to indicate a causal relationship. Our findings align with animal models of experimentally induced myopia in which systemic and ocular application of Mel has been shown to impact on refractive status and ocular shape and suggest that Mel may influence human refractive error and ocular shape . Further research is required to determine the nature of this influence.…”

The chick eye in vision research: An excellent model for the study of ocular disease

“…This was hypothesized to be due to maintenance of normal melatonin secretion rhythms in hooded chicks. Additionally, Wahl et al (2011) demonstrated that giving daily melatonin eye drops to CL chicks was protective against development of hyperopia. Additionally, they found that administering a melatonin hormone blocker, luzidone, caused normal day-night cycle chicks to develop hyperopia.…”

Plasticity in the growth of the chick eye: Emmetropization achieved by alternate morphologies

“…When CL chicks are treated with melatonin eye drops during the subjective night, the eye is protected and grows normally. Conversely, when chicks in normal day/night cycles are treated with the melatonin receptor antagonist luzindole, they develop hyperopia (Li & Howland, 2002; Wahl, Li, Takagi & Howland, 2011). …”

“…While these rhythms have not been established as important factors in normal ocular growth, their absence, correlated with abnormalities in ocular growth, is suggestive. Moreover, when melatonin rhythms are blocked in chicks raised in N conditions, they develop hyperopia (Li & Howland, 2002; Wahl, Li, Takagi & Howland, 2011). …”

“…The morphology and physiological optics of the chick eye are particularly sensitive to fluctuations in melatonin levels during the developmental period (Wahl, Li, Takagi & Howland, 2011). Since melatonin rhythms affect ocular growth (Wiechmann & Summers, 2008), and melatonin rhythms are damped by CL (Li & Howland, 2000, 2002) one can conclude that it is through this damping during development in CL that abnormal ocular growth occurs.…”