Retinal transcriptome of neonatal mice after optic nerve injury

Shi-Qi Yao; Meng Wang; Jia-Jian Liang; Tsz Kin Ng; Ling-Ping Cen

doi:10.1371/journal.pone.0286344

Retinal transcriptome of neonatal mice after optic nerve injury

PLoS One. 2023 May 30;18(5):e0286344. doi: 10.1371/journal.pone.0286344. eCollection 2023.

Authors

Shi-Qi Yao^{1

2}, Meng Wang^{1

2}, Jia-Jian Liang¹, Tsz Kin Ng^{1

2

3}, Ling-Ping Cen^{1

2}

Affiliations

¹ Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong, China.
² Shantou University Medical College, Shantou, Guangdong, China.
³ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.

Abstract

Background: The axonal growth capacity of retinal ganglion cells decreases dramatically within the first day of birth, and the axonal regeneration after injury in mature mammals is very limited. Here, this study aimed to delineate the transcriptomic changes associated with altered axonal growth capacity and to identify the key genes associated with axonal regeneration by the RNA sequencing (RNA-Seq) analysis.

Methods: The whole retinas from the mice of embryonic day (E) 20, postnatal day (P) 1 and P3 were collected at 6 hours after optic nerve crush (ONC). Differentially expressed genes (DEGs) for ONC or ages were identified by the RNA-Seq analysis. K-means analysis was conducted for the clustering of DEGs based on expression patterns. Enrichment of functions and signaling pathways analysis were performed based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and Gene Set Enrichment analysis (GSEA). Quantitative real time polymerase chain reaction (qRT-PCR) was used to validate the DEGs selected from the RNA-Seq analysis.

Results: In total, 5,408 DEGs were identified for ages, and 2,639 DEGs in neonatal mouse retina after ONC. K-means analysis revealed 7 clusters in age-DEGs and 11 clusters in ONC-DEGs. The GO, KEGG and GSEA pathway analyses identified significantly enrichment of DEGs in the visual perception and phototransduction for the age effect, and the break repair, neuron projection guidance, and immune system pathway for the ONC. PPI analysis identified hub genes in the axon-related gene cluster. The expressions of Mlc1, Zfp296, Atoh7, Ecel1, Creb5, Fosb, and Lcn2, thought to be involved in RGC death and axonal growth were validated by qRT-PCR.

Conclusions: This study, for the first time, delineated the gene expression changes following ON injury in embryonic and neonatal mice, providing a new resource of age- and injury-driven data on axonal growth capacity.

Copyright: © 2023 Yao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Gene Expression Profiling
Mammals / genetics
Mice
Optic Nerve Injuries* / genetics
Optic Nerve Injuries* / metabolism
Retina / metabolism
Retinal Ganglion Cells / metabolism
Transcriptome*

Grants and funding

This work was supported by the National Natural Science Foundation of China (project code: 81570849 to L.P.C.) and the Natural Science Foundation of Guangdong Province of China (project code: 2020A1515011413 to L.P.C.), China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.