Data on the role of miR-144 in regulating fetal hemoglobin production in retinal pigmented epithelial cells

Abstract

The data presented in this article are connected to our related article entitled “Inhibiting microRNA-144 potentiates Nrf2-dependent antioxidant signaling in retinal pigmented epithelial cells (RPE) and protects against oxidative stress-induced outer retinal degeneration” [1] where, we have shown that miR-144 induces oxidative stress in RPE cells by targeting Nrf2 expression. Previous studies from our laboratory have shown that like erythroid cells, RPE cells express α, β and γ-globin and produce hemoglobin locally in retina. Further, the ability to therapeutically reactivate fetal hemoglobin production in these cells, a strategy of high potential benefit in the treatment of complications of sickle cell disease, including retinopathy, is impacted by Nrf2-mediated signaling [2,3]. Studies by others [4,5] provide compelling evidence of a regulatory role for miR-144 and Nrf2 in fetal hemoglobin production in erythroid cells. Our current work confirms this finding in human RPE. We additionally show that miR-144-mediated regulation of fetal hemoglobin production in RPE cells is independent of kruppel like factor 1 (KLF-1). This supports the plausibility that in RPE, hemoglobin, particularly fetal hemoglobin, may be important for functions other than oxygen transport (e.g., antioxidant defense). Indeed, our new data on miR-144 in RPE supports strongly the potential mechanistic between fetal hemoglobin production and the regulation of oxidative stress in this cell type [1].

Functions and Diseases of the Retinal Pigment Epithelium

“…Many studies have been conducted on retinal epithelial damage caused by oxidative stress and inflammation, and recent studies have shown that the redox-sensitive microRNA (miR)-144 plays an important role in the regulation of antioxidant signaling pathways in human and mouse RPE. Oxidative stress enhanced the expression of miR-144-3p and mir-144-5p, decreased expression of Nrf2 and downstream antioxidant target genes Nqo1 and Gclc , decreased glutathione levels, and increased RPE cell death ( Yam et al, 2019 ; Jadeja and Martin, 2020 ). In summary, oxidative stress and inflammation cause RPE cell damage, which in turn causes retinal dysfunction and even blindness.…”

Resveratrol and quercetin protect from Benzo(a)pyrene-induced autophagy in retinal pigment epithelial cells

“…Antioxidant levels in cells are reduced in degenerative retinopathy. Many studies on retinal epithelium damage caused by oxidative stress and in ammation have been conducted, and recent studieshave shown that redox-sensitive microRNA (miR) play a signi cant role in the regulation of antioxidant signaling pathways in human and rat RPEs [29]. RPE cell damage is caused by oxidative stress and in ammation, which leads to retinal dysfunction and even blindness.…”

Endogenous and Exogenous Regulation of Redox Homeostasis in Retinal Pigment Epithelium Cells: An Updated Antioxidant Perspective

“…Redox-sensitive miRNAs play an important role in the regulation of antioxidant signaling pathways in the RPE. Recent studies have shown that OS enhances the expression of miR-144-3p and mir-144-5p, which block the expression of Nrf2 and controlled target genes for antioxidants Nqo1 and Gclc, reducing the content of GSH in human and mouse RPE and increasing cell death [ 354 , 355 ]. Nrf2 is a target gene of miR-93; the overexpression of Nrf2 alleviates the high glucose-induced apoptotic effect of ARPE-19 cells and can reverse the pro-apoptotic effect and inflammation of miR-93 [ 356 ].…”