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

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 act...

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Autores principales:	Ling Zeng, Xiaoning Li, Jian Liu, Hong Liu, Heping Xu, Zhikuan Yang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	form deprivation myopic retinopathy animal model RNA sequencing complement cascade ABC transporter Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/3d1d6423edf54a3fac86849cd44f45a0
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spelling	oai:doaj.org-article:3d1d6423edf54a3fac86849cd44f45a02021-11-25T17:58:18ZRNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs10.3390/ijms2222125981422-00671661-6596https://doaj.org/article/3d1d6423edf54a3fac86849cd44f45a02021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12598https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Myopia 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.Ling ZengXiaoning LiJian LiuHong LiuHeping XuZhikuan YangMDPI AGarticleform deprivationmyopic retinopathyanimal modelRNA sequencingcomplement cascadeABC transporterBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12598, p 12598 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	form deprivation myopic retinopathy animal model RNA sequencing complement cascade ABC transporter Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	form deprivation myopic retinopathy animal model RNA sequencing complement cascade ABC transporter Biology (General) QH301-705.5 Chemistry QD1-999 Ling Zeng Xiaoning Li Jian Liu Hong Liu Heping Xu Zhikuan Yang RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
description	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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.
format	article
author	Ling Zeng Xiaoning Li Jian Liu Hong Liu Heping Xu Zhikuan Yang
author_facet	Ling Zeng Xiaoning Li Jian Liu Hong Liu Heping Xu Zhikuan Yang
author_sort	Ling Zeng
title	RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
title_short	RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
title_full	RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
title_fullStr	RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
title_full_unstemmed	RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs
title_sort	rna-seq analysis reveals an essential role of the tyrosine metabolic pathway and inflammation in myopia-induced retinal degeneration in guinea pigs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3d1d6423edf54a3fac86849cd44f45a0
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RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs

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