Transcriptome analysis for UVB‐induced phototoxicity in mouse retina

Abstract

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. K E Y W O R D Sphoto-toxicity, retina, transcriptome, RNA-seq, retinal diseases, UVB

Ablation of SMUG1 Reduces Cell Viability and Increases UVC-Mediated Apoptosis in Hepatocarcinoma HepG2 Cells

“…Deficiencies in DNA repair lead to the accumulation of DNA damage and the development of cancer and premature aging. In a previous study, we found that Smug1 was downregulated in ultraviolet B (UVB)-irradiated mouse retinas compared with control retinas [13]. To test the physiological functions of SMUG1, we generated SMUG1 KO cells using the CRISPR/Cas9 genome engineering system.…”

Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

“…In this research, the retina of 10-week-old mice was exposed to 35 mJ/cm 2 UVB once daily for 4 consecutive days. After 2 days of recovery, the mice were sacrificed and the effect of UVB on the retina was studied [169]. Structurally, no changes were seen in the retinal structures after irradiation, and yet, 126 genes were significantly upregulated while 51 other genes were downregulated in the retinal tissue.…”

“…Structurally, no changes were seen in the retinal structures after irradiation, and yet, 126 genes were significantly upregulated while 51 other genes were downregulated in the retinal tissue. After analysis, these genes can be sorted into 5 categories of genes and the categories were chromatin regulation, stress and signaling, gene expression regulation, RNA processing, and neuronal genes [169]. Based on these categories, it can be seen that UVB does affect gene expression down to the chromosome level and induces cellular stress upon irradiation.…”

Corneal UV Protective Effects of a Topical Antioxidant Formulation: A Pilot Study on In Vivo Rabbits

“…The metabolites of tryptophan within the lens absorb UV radiation, decreasing the amount of light transmitted from the lens [18]. By the early 20s, only 0.1% of UV rays can penetrate, and by the age of 60 years, no UV radiation can reach the retina [19], except in the case of aphakia or pseudophakia [20,21].…”