A biochemical basis for induction of retina regeneration by antioxidants

Abstract

The use of antioxidants in tissue regeneration has been studied, but their mechanism of action is not well understood. Here, we analyze the role of the antioxidant N-acetylcysteine (NAC) in retina regeneration. Embryonic chicks are able to regenerate their retina after its complete removal from retinal stem/progenitor cells present in the ciliary margin (CM) of the eye only if a source of exogenous factors, such as FGF2, is present. This study shows that NAC modifies the redox status of the CM, initiates self-renewal of the stem/progenitor cells, and induces regeneration in the absence of FGF2. NAC works as an antioxidant by scavenging free radicals either independently or through the synthesis of glutathione (GSH), and/or by reducing oxidized proteins through a thiol disulfide exchange activity. We dissected the mechanism used by NAC to induce regeneration through the use of inhibitors of GSH synthesis and the use of other antioxidants with different biochemical structures and modes of action, and found that NAC induces regeneration through its thiol disulfide exchange activity. Thus, our results provide, for the first time, a biochemical basis for induction of retina regeneration. Furthermore, NAC induction was independent of FGF receptor signaling, but dependent on the MAPK (pErk1/2) pathway.

Cell Fate of Retinal Progenitor Cells: In Ovo UbC-StarTrack Analysis

“…The ciliary margin is a developing retinal area with a transitory capability to regenerate a chicken retina [ 3 , 36 , 37 , 38 ]. Most omic studies focused on the central retina without differentiating the specific features of the peripheral retina or the CM.…”

“…CM progenitor cells generate all retinal cell types, but this capability decreases during development [ 35 ]. Furthermore, CM presents a transient regenerative capability during the early stages of development [ 36 , 37 , 38 , 39 ]. These data depict the importance of knowing the biology of CM progenitor cells.…”

“…This is a crucial topic for understanding retinal development and to design successful cell retina replacement therapies. In this respect, multicolor lineage tracing methods are powerful tools for tracing clusters of cells derived from a common RPC [ 36 , 46 ]. In this study, we focused on the derived cell progenies of individual RPCs located in the chicken CM at early developmental time points.…”

Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products

“…Glutathiones are important for hepatic injury and inflammation: Excessive anti-oxidant depletion causes mitochondrial damage and cell-growth arrest in ALF [48]; glutathione replacement by N-acetyl cysteine (NAC) benefits recovery in ALF [41]. Tissue regeneration by NAC (in retina) involved stem/progenitor cell renewal [49]. This was independent of growth factor signaling (FGF) but included MAPK-1 or-3 pathways.…”

Intraperitoneal BromAc® Does Not Interfere with the Healing of Colon Anastomosis

“…Acetylcysteine has also been shown to enhance wound healing [ 27 ], and its mechanisms of action may be due to its antioxidant properties, which quench the reactive species abundant in injured tissues [ 13 ], whilst at the same time enhancing the immune system [ 28 ]. Further, it may also aid in the regeneration of endogenous antioxidants, such as glutathione [ 29 ]. Acetylcysteine is known to enhance the proteolytic action of bromelain and, since wound healing is dependent on debridement, amongst other parameters, such as immune enhancement, the modulation of inflammation, etc., the presence of acetylcysteine may, in fact, enhance the healing process [ 30 ].…”