RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs

Ling Zeng, Xiaoning Li, Jian Liu, Hong Liu, Heping Xu*, Zhikuan Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number12598
JournalInternational Journal of Molecular Sciences
Volume22
DOIs
Publication statusPublished - 22 Nov 2021

Bibliographical note

Funding Information:
Funding: This work was supported by the Key Research and Development Program of Hunan Province (2019SK2051), the Science & Technology Department of Hunan Province (2018RS3123, 2020CB1002) and the Research Fund Project of AIER Eye Hospital Group (AR2003D1, AF1903D4 and AF1903D3).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • ABC transporter
  • Animal model
  • Complement cascade
  • Form deprivation
  • Glycosaminoglycan biosynthesis
  • Lipid biosynthesis
  • Myopic retinopathy
  • RNA sequencing

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs'. Together they form a unique fingerprint.

Cite this