Expression of <i>SCO1</i> and <i>SCO2</i> after form-deprivation myopia in Guinea pigs

Zhou, Guimei; Lan, Chang-Jun; Yang, Qin; Zhong, Weiqi; Gu, Zhonghua; Xia, Xiang; Mao, Yumei; Liao, Xuan

doi:10.1177/11206721211070305

Cited by 3 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cytochrome C was, however, upregulated in LIM while downregulated in FDM. In a previous study with an FDM model of guinea pigs, both protein and mRNA expression levels of cytochrome C protein (SCO1 and SCO2) were found to be considerably lower in the FDM group [43]. The second analysis in Figure 6B represented relative expression levels of all five complex genes.…”

Section: Oxidative Phosphorylation Revealed Specific Alterationsmentioning

confidence: 89%

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Kim,

Lee,

Kim

et al. 2023

Genes

View full text Add to dashboard Cite

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia’s pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways.

show abstract

Section: Oxidative Phosphorylation Revealed Specific Alterationsmentioning

confidence: 89%

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Kim,

Lee,

Kim

et al. 2023

Genes

View full text Add to dashboard Cite

show abstract

“…Several genes were reported to be associated with HM, but classical myopia characteristics such as refractive error change and prolonged axial length were not observed in gene mutant animal models [22,54]. The form deprivation myopia (FDM) was a classical approach to induce a high myopia model and it was successfully established in different animal species, including monkeys, mice, chickens, tree shrews, guinea pigs, and rats [44,[55][56][57][58][59][60]]. To amplify the potential impact of Timp4 knockdown on ocular development, we established a form deprivation model on the three-week-old rats of three genotypes, referring to the previously reported form deprivation models of chicken and rats [45,61] (Figure A2B).…”

Section: Determination Of Ocular Components Under Extra Pressure From...mentioning

confidence: 99%

Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner

Zhou,

Jiang,

et al. 2023

IJMS

View full text Add to dashboard Cite

Thinning of the sclera happens in myopia eyes owing to extracellular matrix (ECM) remodeling, but the initiators of the ECM remodeling in myopia are mainly unknown. The matrix metalloproteinase (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMPs) regulate the homeostasis of the ECM. However, genetic studies of the MMPs and TIMPs in the occurrence of myopia are poor and limited. This study systematically investigated the association between twenty-nine genes of the TIMPs and MMPs families and early-onset high myopia (eoHM) based on whole exome sequencing data. Two TIMP4 heterozygous loss-of-function (LoF) variants, c.528C>A in six patients and c.234_235insAA in one patient, were statistically enriched in 928 eoHM probands compared to that in 5469 non-high myopia control (p = 3.7 × 10−5) and that in the general population (p = 2.78 × 10−9). Consequently, the Timp4 gene editing rat was further evaluated to explore the possible role of Timp4 on ocular and myopia development. A series of ocular morphology abnormalities in a dose-dependent manner (Timp4−/− < Timp4+/− < Timp4+/+) were observed in a rat model, including the decline in the retinal thickness, the elongation in the axial length, more vulnerable to the form deprivation model, morphology changes in sclera collagen bundles, and the decrease in collagen contents of the sclera and retina. Electroretinogram revealed that the b-wave amplitudes of Timp4 defect rats were significantly reduced, consistent with the shorter length of the bipolar axons detected by HE and IF staining. Heterozygous LoF variants in the TIMP4 are associated with early onset high myopia, and the Timp4 defect disturbs ocular development by influencing the morphology and function of the ocular tissue.

show abstract

“…Recent studies have shown that RGCs may be involved in the occurrence and development of myopia. Clinical studies and animal experiments have confirmed that myopia can cause a decrease in the number of RGCs [ 19 , 20 ]. Early-onset high myopia can cause abnormal axonal projection of RGCs [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

Wang,

Lin,

Liu

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Background Long noncoding RNAs (lncRNAs) play a key role in the occurrence and progression of myopia. However, the function of lncRNAs in retinal ganglion cells (RGCs) in the pathogenesis of myopia is still unknown. The aim of our study was to explore the lncRNA-mediated competing endogenous RNA (ceRNA) network in RGCs during the development of myopia. Methods RNA sequencing was performed to analyze lncRNA and mRNA expression profiles in RGCs between guinea pigs with form-deprived myopia (FDM) and normal control guinea pigs, and related ceRNA networks were constructed. Then, potentially important genes in ceRNA networks were verified by qRT‒PCR, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore biological functions in the RGCs of FDM guinea pigs. The important genes and related signaling pathways were further verified by qRT‒PCR, immunohistochemistry, immunofluorescence and Western blot in myopia in FDM guinea pigs, FDM mice, and highly myopic adults. Results The distribution of RGCs was uneven, the number of RGCs was decreased, and RGC apoptosis was increased in FDM guinea pigs. In total, 873 lncRNAs and 2480 mRNAs were determined to be differentially expressed genes in RGCs from normal control and FDM guinea pigs. Via lncRNA-mediated ceRNA network construction and PCR verification, we found that lncRNA-XR_002792574.1 may be involved in the development of myopia through the miR-760-3p/Adcy1 pathway in RGCs. Further verification in FDM guinea pigs, FDM mice, and highly myopic adults demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to cGMP/PKG, the apelin signaling pathway and scleral remodeling. Conclusion We demonstrated that the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis in RGCs might be related to myopia. On the one hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis might inhibit the cGMP/PKG and apelin signaling pathways in RGCs, thereby causing RGC damage in myopia. On the other hand, the lncRNA-XR_002792574.1/miR-760-3p/Adcy1 axis may cause myopic scleral remodeling through the ERK-MMP-2 pathway. These findings may reveal novel potential targets in myopia and provide reference value for exploration and development of gene editing therapeutics for hereditary myopia.

show abstract

Expression of SCO1 and SCO2 after form-deprivation myopia in Guinea pigs

Cited by 3 publications

References 40 publications

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice

Defect of TIMP4 Is Associated with High Myopia and Participates in Rat Ocular Development in a Dose-Dependent Manner

LncRNA-XR_002792574.1-mediated ceRNA network reveals potential biomarkers in myopia-induced retinal ganglion cell damage

Contact Info

Product

Resources

About