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Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth.

ABSTRACT: Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and causes myopia, whereas myopic defocus imposed by positive lenses slows eye growth and produces a compensatory hyperopic shift in refractive state. The balance between these two optical signals is thought to regulate refractive eye development; however, the ability of the retina to recognize the sign of optical defocus and the composition of molecular signaling pathways guiding emmetropization are the subjects of intense investigation and debate. We found that the retina can readily distinguish between imposed myopic and hyperopic defocus, and identified key signaling pathways underlying retinal response to the defocus of different signs. Comparison of retinal transcriptomes in common marmosets exposed to either myopic or hyperopic defocus for 10 days or 5 weeks revealed that the primate retina responds to defocus of different signs by activation or suppression of largely distinct pathways. We also found that 29 genes differentially expressed in the marmoset retina in response to imposed defocus are localized within human myopia quantitative trait loci (QTLs), suggesting functional overlap between genes differentially expressed in the marmoset retina upon exposure to optical defocus and genes causing myopia in humans. These findings identify retinal pathways involved in the development of myopia, as well as potential new strategies for its treatment.

SUBMITTER: Tkatchenko TV

PROVIDER: S-EPMC6177118 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth.

Tkatchenko Tatiana V TV Troilo David D Benavente-Perez Alexandra A Tkatchenko Andrei V AV

PLoS biology 20181009 10

Myopia (nearsightedness) is the most common eye disorder, which is rapidly becoming one of the leading causes of vision loss in several parts of the world because of a recent sharp increase in prevalence. Nearwork, which produces hyperopic optical defocus on the retina, has been implicated as one of the environmental risk factors causing myopia in humans. Experimental studies have shown that hyperopic defocus imposed by negative power lenses placed in front of the eye accelerates eye growth and ...[more]

PMID: 30300342

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Project description:BackgroundIn the past decade and during the COVID pandemic, the prevalence of myopia has reached epidemic proportions. To address this issue and reduce the prevalence of myopia and its complications, it is necessary to develop more effective interventions for controlling myopia. In this study, we investigated the combined effects of narrowband lights and competing defocus on eye growth and refraction in chicks, an important step in understanding the potential for these interventions to control myopia. This is the first time these effects have been characterized.MethodsThree groups of five-day-old chicks (n = 8 per group) were raised in three different lighting conditions: white, red, and blue for 13 days in a 12/12-h light/dark diurnal cycle. One eye was randomly selected for applications of a dual-power optical lens (- 10 D/ + 10 D, 50∶50), while another eye was left untreated as control. Vitreous chamber depth (VCD), axial length (AL), choroidal thickness (CT) and refractive errors were measured at pre-exposure (D0) and following 3 (D3), 7 (D7), 10 (D10), and 13 days (D13) of light exposure.ResultsUnder white light, the dual-power lens induced a hyperopic shift [at D13, mean spherical equivalent refraction (SER), treated vs. control: 4.81 ± 0.43 D vs. 1.77 ± 0.21 D, P < 0.001] and significantly reduced the progression of axial elongation (at D13, change in AL, treated vs. control: 1.25 ± 0.04 mm vs. 1.45 ± 0.05 mm, P < 0.01). Compared to white light alone, blue light alone induced a hyperopic shift (at D13, mean SER, blue vs. white: 2.75 ± 0.21 D vs. 1.77 ± 0.21 D, P < 0.01) and significantly reduced axial elongation (at D13, change in AL, blue vs. white: 1.17 ± 0.06 mm vs. 1.45 ± 0.05 mm, P < 0.01) in control eyes. When comparing all conditions, eyes exposed to blue light plus dual-power lens had the least axial elongation (at D13, change in AL, 0.99 ± 0.05 mm) and were the most hyperopic (at D13, mean SER, 6.36 ± 0.39 D).ConclusionsBoth narrowband blue light and dual-power lens interventions were effective in inducing a hyperopic shift in chicks, and provided protection against myopia development. The combination of these interventions had additive effects, making them potentially even more effective. These findings support the use of optical defocus interventions in combination with wavelength filters in clinical studies testing their effectiveness in treating myopia in children.

Dataset Information

Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth.

Publications

Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth.

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