Abstract
Background: Myopia is the second leading cause of visual impairment globally. Myopia can induce sight-threatening retinal degeneration and the underlying mechanism remains poorly defined. We generated a model of myopia-induced early-stage retinal degeneration in guinea pigs and investigated the mechanism of action. Methods: The form-deprivation-induced myopia (FDM) was induced in the right eyes of 2~3-week-old guinea pigs using a translucent balloon for 15 weeks. The left eye remained untreated and served as a self-control. Another group of untreated age-matched animals was used as naïve controls. The refractive error and ocular biometrics were measured at 3, 7, 9, 12 and 15 weeks post-FDM induction. Visual function was evaluated by electroretinography. Retinal neurons and synaptic structures were examined by confocal microscopy of immunolabelled retinal sections. The total RNAs were extracted from the retinas and processed for RNA sequencing analysis. Results: The FDM eyes presented a progressive axial length elongation and refractive error development. After 15 weeks of intervention, the average refractive power was −3.40 ± 1.85 D in the FDM eyes, +2.94 ± 0.59 D and +2.69 ± 0.56 D in the self-control and naïve control eyes, respectively. The a-wave amplitude was significantly lower in FDM eyes and these eyes had a significantly lower number of rods, secretagogin+ bipolar cells, and GABAergic amacrine cells in selected retinal areas. RNA-seq analysis showed that 288 genes were upregulated and 119 genes were downregulated in FDM retinas compared to naïve control retinas. In addition, 152 genes were upregulated and 12 were downregulated in FDM retinas compared to self-control retinas. The KEGG enrichment analysis showed that tyrosine metabolism, ABC transporters and inflammatory pathways were upregulated, whereas tight junction, lipid and glycosaminoglycan biosynthesis were downregulated in FDM eyes. Conclusions: The long-term (15-week) FDM in the guinea pig models induced an early-stage retinal degeneration. The dysregulation of the tyrosine metabolism and inflammatory pathways may contribute to the pathogenesis of myopia-induced retinal degeneration.
Highlights
Myopia is the leading cause of preventable visual impairment in children globally [1]
The axial length increased with age in all groups during the course of the study with the highest increments observed in the form-deprivation-induced myopia (FDM) group (Table 1)
The axial length in the FDM group was significantly negatively correlated with the changes in refractive error (p < 0.05; r2 = 0.456) but positively correlated with the changes in vitreous chamber depth (VCD) (p < 0.05; r2 = 0.451)
Summary
Myopia (short-sightedness) is the leading cause of preventable visual impairment in children globally [1]. A more recent study reported that ~70% of Japanese aged between 34–59 years old have myopia and the incidence of high myopia is ~10% [6]. In China, the incidence of myopia among individuals who were born after the 1960s reached a peak of 80% in the 1980s and a recent retrospective study reported the myopia prevalence had increased from 23.13% in 5 years old to 82.83% in 11-year-old schoolchildren [7]. We generated a model of myopia-induced early-stage retinal degeneration in guinea pigs and investigated the mechanism of action. The KEGG enrichment analysis showed that tyrosine metabolism, ABC transporters and inflammatory pathways were upregulated, whereas tight junction, lipid and glycosaminoglycan biosynthesis were downregulated in FDM eyes. Conclusions: The long-term (15-week) FDM in the guinea pig models induced an early-stage retinal degeneration. The dysregulation of the tyrosine metabolism and inflammatory pathways may contribute to the pathogenesis of myopia-induced retinal degeneration
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