Transcriptome analysis for UVB‐induced phototoxicity in mouse retina

• Published in: Environmental toxicology Vol. 33; no. 1; pp. 52 - 62
• Main Authors: An, Mi‐Jin, Kim, Chul‐Hong, Nam, Gyu‐You, Kim, Dae‐Hyun, Rhee, Sangmyung, Cho, Sung‐Jin, Kim, Jung‐Woong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018
• Subjects: Animals; Blindness; Cell activation; Cell death; Cellular stress response; Chromatin; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; DNA; Dopamine D1 receptors; Down-Regulation - radiation effects; Exposure; Eye (anatomy); Gene expression; Gene Expression Profiling; Genes; Identification; Irradiation; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nucleic acids; Nucleotide sequence; PCR; People with disabilities; Period 1 protein; Phototoxicity; photo‐toxicity; Principal Component Analysis; Radiation; Real-Time Polymerase Chain Reaction; Receptors, N-Methyl-D-Aspartate - genetics; Receptors, N-Methyl-D-Aspartate - metabolism; Retina; Retina - cytology; Retina - metabolism; Retina - radiation effects; retinal diseases; Retinoid X receptor α; Ribonucleic acid; RNA; RNA - chemistry; RNA - isolation & purification; RNA - metabolism; RNA processing; RNA‐seq; Sequence Analysis, RNA; Signal Transduction - radiation effects; Signaling; SUMO protein; Transcription; Transcription factors; transcriptome; Transcriptome - radiation effects; Ultraviolet radiation; Ultraviolet Rays; Up-Regulation - radiation effects; UVB; Vision; UVB; retinal diseases; photo-toxicity; RNA-seq; retina; transcriptome
• ISSN: 1520-4081; 1522-7278
• DOI: 10.1002/tox.22494

Throughout life, the human eye is continuously exposed to sunlight and artificial lighting. Ambient light exposure can lead to visual impairment and transient or permanent blindness. To mimic benign light stress conditions, Mus musculus eyes were exposed to low‐energy UVB radiation, ensuring no severe morphological changes in the retinal structure post‐exposure. We performed RNA‐seq analysis to reveal the early transcriptional changes and key molecular pathways involved before the activation of the canonical cell death pathway. RNA‐seq analysis identified 537 genes that were differentially modulated, out of which 126 were clearly up regulated (>2‐fold, P < .01) and 51 were significantly down regulated (<2‐fold, P < .01) in response to UVB irradiation in the mouse retina. Gene ontology analysis revealed that UVB exposure affected pathways for cellular stress and signaling (eg, Creb3, Ddrgk1, Grin1, Map7, Uqcc2, Uqcrb), regulation of chromatin and gene expression (eg, Chd5, Jarid2, Kat6a, Smarcc2, Sumo1, Zfp84), transcription factors (eg, Asxl2, Atf7, Per1, Phox2a, Rxra), RNA processing, and neuronal genes (eg, B4gal2, Drd1, Grm5, Rnf40, Rnps1, Usp39, Wbp4). The differentially expressed genes from the RNA‐seq analysis were validated by quantitative PCR. Both analyses yielded similar gene expression patterns. The genes and pathways identified here improve the understanding of early transcriptional responses to UVB irradiation. They may also help in elucidating the genes responsible for the inherent susceptibility of humans to UVB‐induced retinal diseases.