Abstract
BackgroundRefractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia. However, it is still largely unknown how optical defocus is detected by the retina.MethodsHere, we used genome-wide RNA-sequencing to conduct analysis of the retinal gene expression network underlying contrast perception and refractive eye development.ResultsWe report that the genetic network subserving contrast perception plays an important role in optical defocus detection and emmetropization. Our results demonstrate an interaction between contrast perception, the retinal circadian clock pathway and the signaling pathway underlying optical defocus detection. We also observe that the relative majority of genes causing human myopia are involved in the processing of optical defocus.ConclusionsTogether, our results support the hypothesis that optical defocus is perceived by the retina using contrast as a proxy and provide new insights into molecular signaling underlying refractive eye development.
Highlights
Refractive eye development is regulated by optical defocus in a process of emmetropization
Contrast sensitivity and susceptibility to form‐deprivation myopia exhibit strong interdependence in mice To investigate the role of contrast in defocus perception and refractive eye development, we analyzed the relationship between contrast sensitivity, baseline refractive error, and susceptibility to form-deprivation myopia in eight genetically diverse strains of mice comprising collaborative cross, i.e., 129S1/svlmj, A/J, C57BL/6J, CAST/ EiJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, and WSB/EiJ mice, at P40-P45
Analysis of baseline refractive errors and susceptibility to form-deprivation myopia in these mice (Fig. 1A, B; Additional file 1: Tables S1 and S2) revealed that both parameters were clearly influenced by the differences in genetic background between the strains (ANOVArefractive error, F(7, 145) = 429.8, p < 0.00001; ANOVAmyopia, F(7, 48) = 9.8, p < 0.00001) and both baseline refractive error and susceptibility to form-deprivation myopia were inherited as quantitative traits, correlation between baseline refractive error and susceptibility to myopia was weak (r = 0.2686, p = 0.0305; Additional file 2: Figure S1)
Summary
Refractive eye development is regulated by optical defocus in a process of emmetropization. Excessive exposure to negative optical defocus often leads to the development of myopia It is still largely unknown how optical defocus is detected by the retina. The role of optical defocus in refractive eye development is a well-established fact, it is still largely unknown how optical defocus is perceived by the retina. It was demonstrated that accommodation and emmetropization are driven by low spatial frequencies even in species with high visual acuity [54, 55]; and the peripheral retina, which has much lower visual acuity than the central retina [56,57,58,59,60,61], plays an important role in defocus detection and emmetropization [8, 22, 24, 62]. Retinae of many species adapted asymmetric photoreceptor distribution which maximizes contrast perception across visual space in expense of other important visual functions such as visual acuity and color perception [70, 71, 76,77,78,79,80,81]
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