Ikelle Larissa, Naash Muna I, Al-Ubaidi Muayyad R
Department of Biomedical Engineering, University of Houston, Houston, TX 77004, USA.
Antioxidants (Basel). 2021 Oct 12;10(10):1595. doi: 10.3390/antiox10101595.
Retinal oxidative stress is a common secondary feature of many retinal diseases. Though it may not be the initial insult, it is a major contributor to the pathogenesis of highly prevalent retinal dystrophic diseases like macular degeneration, diabetic retinopathy, and retinitis pigmentosa. We explored the role of superoxide dismutase 3 (SOD3) in retinal homeostasis since SOD3 protects the extracellular matrix (ECM) from oxidative injury. We show that SOD3 is mainly extracellularly localized and is upregulated as a result of environmental and pathogenic stress. Ablation of SOD3 resulted in reduced functional electroretinographic responses and number of photoreceptors, which is exacerbated with age. By contrast, overexpression showed increased electroretinographic responses and increased number of photoreceptors at young ages, but appears deleterious as the animal ages, as determined from the associated functional decline. Our exploration shows that SOD3 is vital to retinal homeostasis but its levels are tightly regulated. This suggests that SOD3 augmentation to combat oxidative stress during retinal degenerative changes may only be effective in the short-term.
视网膜氧化应激是许多视网膜疾病常见的继发性特征。尽管它可能不是最初的损伤因素，但它是黄斑变性、糖尿病视网膜病变和视网膜色素变性等高度流行的视网膜营养不良性疾病发病机制的主要促成因素。由于超氧化物歧化酶3（SOD3）可保护细胞外基质（ECM）免受氧化损伤，我们探讨了其在视网膜内环境稳态中的作用。我们发现SOD3主要定位于细胞外，并且会因环境和致病应激而上调。敲除SOD3会导致视网膜电图功能反应降低和光感受器数量减少，且这种情况会随着年龄的增长而加剧。相比之下，过表达则显示在年轻时视网膜电图反应增加且光感受器数量增多，但随着动物年龄增长，从相关的功能衰退来看，这似乎是有害的。我们的研究表明，SOD3对视网膜内环境稳态至关重要，但其水平受到严格调控。这表明在视网膜退行性变化期间增加SOD3以对抗氧化应激可能仅在短期内有效。
