Abstract
The Retinal Ion-Driven Fluid Efflux (RIDE) model theorizes that phototransduction-driven changes in trans-retinal ion and fluid transport underlie the development of myopia (short-sightedness). In support of this model, previous functional studies have identified the attenuation of outer retinal contributions to the global flash electroretinogram (gfERG) following weeks of myopia induction in chicks, while discovery-driven transcriptome studies have identified changes to the expression of ATP-driven ion transport and mitochondrial metabolism genes in the retina/RPE/choroid at the mid- to late-induction time-points. Less is known about the early time-points despite biometric analyses demonstrating changes in eye growth by 3 h in the chick lens defocus model. Thus, the present study compared gfERG and transcriptome profiles between 3 h and 3 days of negative lens-induced myopia and positive lens-induced hyperopia in chicks. Photoreceptor (a-wave and d-wave) and bipolar (b-wave and late-stage d-wave) cell responses were suppressed following negative lens-wear, particularly at the 3–4 h and 3-day time-points when active shifts in the rate of ocular growth were expected. Transcriptome measures revealed the up-regulation of oxidative phosphorylation genes following 6 h of negative lens-wear, concordant with previous reports at 2 days in this model. Signal transduction pathways, with core genes involved in glutamate and G-protein coupled receptor signalling, were down-regulated at 6 h. These findings contribute to a growing body of evidence for the dysregulation of phototransduction and mitochondrial metabolism in animal models of myopia.
Highlights
Myopia and hyperopia occur when the eye is too long or short, respectively, for its refractive power
Myopia significantly increases the risk of vision loss from degenerative secondary disorders [3,4,5], making it a priority to understand the mechanisms underpinning ocular growth regulation
Using high throughput transcriptomics and proteomics, we recently identified changes in the expression of genes and proteins involved in phototransduction and cellular metabolism as key molecular features of the retina/RPE response during the first 6 h of refractive error induction and recovery in chicks [25,26]
Summary
Myopia (short-sightedness) and hyperopia (long-sightedness) occur when the eye is too long or short, respectively, for its refractive power. 34% of the worldwide population are myopic, with prevalence expected to reach 50% by 2050 [1,2]. Myopia significantly increases the risk of vision loss from degenerative secondary disorders [3,4,5], making it a priority to understand the mechanisms underpinning ocular growth regulation. Ocular growth has been shown to be controlled locally by the retina in a process that is dependent on visual feedback [6]. The biological mechanisms involved in the retinal control of eye growth are unresolved, though several models exist postulating roles for various signalling molecules and cell types [7,8,9].
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