title: RNA sequence reveals mouse retinal transcriptome changes early after axonal injury.
abstract: Glaucoma is an ocular disease characterized by progressive retinal ganglion cell (RGC) death caused by axonal injury. However, the underlying mechanisms involved in RGC death remain unclear. In this study, we investigated changes in the transcriptome profile following axonal injury in mice (C57BL/6) with RNA sequencing (RNA-seq) technology. The experiment group underwent an optic nerve crush (ONC) procedure to induce axonal injury in the right eye, and the control group underwent a sham procedure. Two days later, we extracted the retinas and performed RNA-seq and a pathway analysis. We identified 177 differentially expressed genes with RNA-seq, notably the endoplasmic reticulum (ER) stress-related genes Atf3, Atf4, Atf5, Chac1, Chop, Egr1 and Trb3, which were significantly upregulated. The pathway analysis revealed that ATF4 was the most significant upstream regulator. The antioxidative response-related genes Hmox1 and Srxn1, as well as the immune response-related genes C1qa, C1qb and C1qc, were also significantly upregulated. To our knowledge, this is the first reported RNA-seq investigation of the retinal transcriptome and molecular pathways in the early stages after axonal injury. Our results indicated that ER stress plays a key role under these conditions. Furthermore, the antioxidative defense and immune responses occurred concurrently in the early stages after axonal injury. We believe that our study will lead to a better understanding of and insight into the molecular mechanisms underlying RGC death after axonal injury.
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Morin
authors.initials: M
authors.lastname: Ryu
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuda
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D008297:Male; D051379:Mice; D020221:Optic Nerve Injuries / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014157:Transcription Factors