Zinflou Corinne, Rochette Patrick J
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec - Université Laval, Hôpital du Saint-Sacrement, Québec, QC, Canada; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec, QC, Canada.
Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec - Université Laval, Hôpital du Saint-Sacrement, Québec, QC, Canada; Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Université Laval, Québec, QC, Canada; Département d'Ophtalmologie et ORL - chirurgie cervico-faciale, Université Laval, Québec, QC, Canada.
Free Radic Biol Med. 2017 Jul;108:118-128. doi: 10.1016/j.freeradbiomed.2017.03.022. Epub 2017 Mar 22.
Exposure to sunlight ultraviolet-A (UVA), the main component of solar UV reaching the eyes, is suspected to play an important part in the onset of ocular pathologies. UVA primary biological deleterious effects arise from the photo-induction of oxidative stress in cells. However, the molecular bases linking UVA-induced oxidation to UVA toxicity in eyes remain poorly understood, especially with regards to the cornea. To shed some light on this issue, we have investigated the susceptibility and response potential of the different corneal cellular layers (epithelium, stroma and endothelium) to UVA-induced oxidation. We have monitored UVA-induced immediate effects on cellular redox balance, on mitochondrial membrane potential, on 8-Hydroxy-2'-deoxyguanosine (8-OHdG) accumulation in cellular DNA and on S-glutathionylated proteins (PSSG) levels along whole rabbit corneas. Higher redox imbalance was observed in the posterior part of the cornea following irradiation. Conversely, UVA-altered mitochondrial membrane potentials were observed only in anterior portions of the cornea. UVA-induced 8-OHdG were found in nuclear DNA of epithelia, while they were found in both nuclear and mitochondrial DNA in stromal and endothelial cells. Finally, significantly higher levels of cytosolic PSSG were measured in epithelia and endothelia immediately after UVA exposure, but not in stromas. Taken together, our findings indicate that while corneal epithelial cells are subjected to important modifications in response to UVA exposure, they efficiently limit the early manifestations of UVA-induced toxicity. On the other hand, the corneal endothelium is more susceptible to UVA-induced oxidation-related toxicity.
暴露于阳光中的紫外线 A（UVA），即到达眼睛的太阳紫外线的主要成分，被怀疑在眼部疾病的发病过程中起重要作用。UVA 的主要生物有害作用源于细胞中氧化应激的光诱导。然而，将 UVA 诱导的氧化与眼睛中的 UVA 毒性联系起来的分子基础仍知之甚少，尤其是在角膜方面。为了阐明这个问题，我们研究了不同角膜细胞层（上皮细胞、基质细胞和内皮细胞）对 UVA 诱导氧化的敏感性和反应潜力。我们监测了 UVA 对整个兔角膜细胞氧化还原平衡、线粒体膜电位、细胞 DNA 中 8-羟基-2'-脱氧鸟苷（8-OHdG）积累以及 S-谷胱甘肽化蛋白（PSSG）水平的即时影响。照射后在角膜后部观察到更高的氧化还原失衡。相反，仅在角膜前部观察到 UVA 改变的线粒体膜电位。UVA 诱导的 8-OHdG 在角膜上皮细胞核 DNA 中被发现，而在基质细胞和内皮细胞的核 DNA 和线粒体 DNA 中均有发现。最后，在 UVA 照射后立即在上皮细胞和内皮细胞中测量到显著更高水平的胞质 PSSG，但在基质细胞中未检测到。综上所述，我们的研究结果表明，虽然角膜上皮细胞在暴露于 UVA 时会发生重要改变，但它们有效地限制了 UVA 诱导毒性的早期表现。另一方面，角膜内皮细胞更容易受到 UVA 诱导的氧化相关毒性的影响。
