Transcription Factor Nfat5/ TonEBP Regulates Photoreceptor Degeneration by Controlling the Inflammatory Signal in Retina 2334

Abstract Description Retinal degeneration (RD) is a serious irreversible condition that leads to blindness. Neuroinflammation is a critical mechanism of the RD progression which could exacerbate the photoreceptor cell death during RD. Nfat5 is a transcription factor of the cytokines that could release the cytokines from the immune cells. However, Nfat5’s role in retinal cells for retinal inflammation and cell death is unknown. Using Nfat5(+/-) mice, we induced RD by NaIO3 injection and performed qPCR array and real-time PCR to evaluate expression change of the inflammatory genes. The photoreceptor cell death was examined via the Western blot method. To identify the Nfat5 role in the glial cells, we cultured microglial cells and Müller glial cells to measure the inflammatory genes in each cell type depending on the expression of the NFAT5. The RNA sequencing results indicated that the Nfat5 was increased during RD development. Nfat5(+/-) mice were more prone to RD development as evidenced by caspase-3 activity in retina tissue, accompanied by higher Tnf and Fasl. Through the PCR results from the retina and in-vitro retinal glial cell culture, we found that Nfat5 promoted the transcription of inflammatory (IL-1, IL-6) and anti-inflammatory cytokines (IL10). Therefore, we suggest that NFAT5 is important for photoreceptor survival, via controlling the inflammatory process of the glial cells during RD. Funding Sources This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2024-00407321). Topic Categories Neuroimmunology (NEUR)