Abstract
In the context of ocular development and eye growth regulation, retinal defocus and/or image contrast appear key variables although the nature of the signal(s) relayed from the retina to the sclera remains poorly understood. Nonetheless, under optimal visual conditions, eye length is brought into alignment with its optical power to achieve approximate emmetropia, through appropriate adjustment to eye growth. The retinal pigment epithelium (RPE), which lies between the retina and choroid/sclera, appears to play a crucial role in this process. In the investigations reported here, we used a chick model system to assess the threshold duration of exposure to lens-imposed defocus and form-deprivation necessary for conversion of evoked retinal signals into changes in BMP gene expression in the RPE. Our study provides evidence for the following: 1) close-loop, optical defocus-guided (negative and positive lenses) bidirectional BMP gene expression regulation, 2) open-loop, form-deprivation (diffusers)-induced down-regulation of BMP gene expression, and 3) early, transient up-regulation of BMP gene expression in response to both types of lens and diffuser applications. The critical exposure for accurately encoding retinal images as biological signals at the level of the RPE is in the order of minutes to hours, depending on the nature of the visual manipulations.
Highlights
While dysregulated eye growth may be the result of genetically programmed altered growth, there is strong evidence for visual environmental influences and gene-environment interactions[2,3,4]
For the three genes of interest, BMP2, BMP4, and BMP7, baseline expression levels were measured in retinal pigment epithelium (RPE) from untreated chicks that matched in age, those subjected to monocular visual manipulations
Using young chicks as an animal model of ocular growth regulation combined with visual manipulations to perturb normal emmetropization, we obtained further supporting evidence for roles of bone morphogenetic proteins (BMPs) and the RPE, as part of a presumed retina-sclera growth modulating signaling cascade
Summary
While dysregulated eye growth may be the result of genetically programmed altered growth, there is strong evidence for visual environmental influences and gene-environment interactions[2,3,4]. Convincing evidence for visual environmental influences on postnatal eye growth regulation is provided by experiments encompassing a range of animal models, including chick, guinea pig, tree shrew, and monkey, and three types of visual manipulations, form-deprivation, in which retinal image contrast is attenuated across some or all spatial frequencies, and optical defocus, in which lenses are used to shift the optical plane of focus for distant objects relative to the retina, either behind it (negative lenses) or in front of it (positive lenses) (Fig. 1)[2]. New insights include: (1) BMP gene expression is down-regulated by form-deprivation (diffusers), as with negative lenses, (2) BMP gene expression shows early, transient up-regulation in response to all treatments, both positive and negative lenses, and diffusers, and (3) there are critical visual stimulus-dependent differences in minimum exposure durations required for generating consistent biological signals at the level of the RPE gene expression, ranging from minutes to hours
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