Functions of glutaredoxin 2 (Grx2) in the retina: Mechanisms and Protection




Tran, Myhoa
Yu, Yu
Wu, Hongli


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Purpose: Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase that reduces S-glutathionylated proteins. Previously, we found that Grx2 could protect the retina from light-induced retinal degeneration (LIRD). However, the mechanisms that coordinate thiol-repair processes in the damaged retina remain unknown. To better understand the protective effects of Grx2, our study was extended to analyze the transcriptome changes of retinal tissue in light-exposed Grx2 knockout (KO) mice. Methods: Wild type (WT) and Grx2 KO mice were exposed to white light at 23,000 lux for 1 hour after dark adaptation for 10 hours. Retinal damage confirmed by electroretinogram (ERG) and spectral domain optical coherence tomography (SD-OCT). The transcriptome of the retinal tissue in WT and Grx2 KO mice were compared using transcriptome shotgun sequencing (RNA-seq). DESeq2 software utilized to analyze gene network. Real-time PCR and Western Blot further confirmed the genes of interest. Results: Light-exposed Grx2 KO mice showed compromised visual function indicated by loss of a- and b-wave amplitudes and thinning of the outer nuclear layer (ONL). Thousands of genes identified with statistically significant expression changes and were then classified into cellular processes and molecular pathways. Among these pathways, many genes that contribute to complement activation, inflammation, and cell survival system were significantly upregulated. Conclusions: Our results suggest that Grx2 could protect the retina from LIRD. Grx2 plays an important role in regulating light-induced retinal inflammation which may be associated with its ability to repair S-glutathionylated substrates.