Investigative ophthalmology & visual science · 2025
Nkx3.2 Inhibits Retinal Degeneration by Modulating Inflammation and Cell Death in RPE.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Park Minsun, Choi Seung-Won, Jeong Da-Un, Shin Hae-Sol, Han Jiyeon, Oh Hye-Kyoung, Jang Jun-Ho, Ryu Nari, Jeong Hyunjin, Song Young-Do, Seo Kyoung Yul, Lee Sanghyuk, Kim Dae-Won
Аннотация
PURPOSE: To identify the expression of Nkx3.2 in retinal pigment epithelium (RPE) and evaluate its physiological role in association with retinal degeneration.
METHODS: Nkx3.2 expression in RPE was examined by biochemical and histological analyses. Various in vitro and in vivo assays were employed to reveal the molecular mechanisms by which Nkx3.2 regulates inflammatory responses and cell survival in RPE. In addition, by investigating multiple animal models, the biological significance of Nkx3.2 in retinal degeneration was assessed.
RESULTS: Nkx3.2 expression was verified in human cadaveric and mouse eye tissues and shown to be regulated by aging and oxidative stress. Mouse model analyses demonstrated retina protection activity of Nkx3.2 against aging, oxidative stress, vascular endothelial growth factor (VEGF) hyperactivation, and laser-induced damage. In vitro studies showed that Nkx3.2 downregulates pro-inflammatory cytokines and chemokines, but it upregulates anti-inflammatory factors. In addition, Nkx3.2 induced proteasomal degradation of receptor-interacting protein kinase 3 (RIP3), which, in turn, inhibited necroptosis. Consistent with these results, transcriptome analysis of mouse retina tissues indicated that Nkx3.2 can modulate gene expression profiles related to inflammatory responses, cell death, and visual function under oxidative stress.
CONCLUSIONS: Nkx3.2 can suppress inflammatory responses and necroptic cell death in RPE. By employing these mechanisms, Nkx3.2 may play a significant role in inhibiting retinal degeneration caused by aging and oxidative stress.
METHODS: Nkx3.2 expression in RPE was examined by biochemical and histological analyses. Various in vitro and in vivo assays were employed to reveal the molecular mechanisms by which Nkx3.2 regulates inflammatory responses and cell survival in RPE. In addition, by investigating multiple animal models, the biological significance of Nkx3.2 in retinal degeneration was assessed.
RESULTS: Nkx3.2 expression was verified in human cadaveric and mouse eye tissues and shown to be regulated by aging and oxidative stress. Mouse model analyses demonstrated retina protection activity of Nkx3.2 against aging, oxidative stress, vascular endothelial growth factor (VEGF) hyperactivation, and laser-induced damage. In vitro studies showed that Nkx3.2 downregulates pro-inflammatory cytokines and chemokines, but it upregulates anti-inflammatory factors. In addition, Nkx3.2 induced proteasomal degradation of receptor-interacting protein kinase 3 (RIP3), which, in turn, inhibited necroptosis. Consistent with these results, transcriptome analysis of mouse retina tissues indicated that Nkx3.2 can modulate gene expression profiles related to inflammatory responses, cell death, and visual function under oxidative stress.
CONCLUSIONS: Nkx3.2 can suppress inflammatory responses and necroptic cell death in RPE. By employing these mechanisms, Nkx3.2 may play a significant role in inhibiting retinal degeneration caused by aging and oxidative stress.