Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Center for Advanced Professional Excellence, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Nutrients. 2020 Nov 27;12(12):3651. doi: 10.3390/nu12123651.
Cataracts account for over half of global blindness. Cataracts formations occur mainly due to aging and to the direct insults of oxidative stress and inflammation to the eye lens. The nuclear factor-erythroid-2-related factor 2 (Nrf2), a transcriptional factor for cell cytoprotection, is known as the master regulator of redox homeostasis. Nrf2 regulates nearly 600 genes involved in cellular protection against contributing factors of oxidative stress, including aging, disease, and inflammation. Nrf2 was reported to disrupt the oxidative stress that activates Nuclear factor-κB (NFκB) and proinflammatory cytokines. One of these cytokines is matrix metalloproteinase 9 (MMP-9), which participates in the decomposition of lens epithelial cells (LECs) extracellular matrix and has been correlated with cataract development. Thus, during inflammatory processes, MMP production may be attenuated by the Nrf2 pathway or by the Nrf2 inhibition of NFκB pathway activation. Moreover, plant-based polyphenols have garnered attention due to their presumed safety and efficacy, nutritional, and antioxidant effects. Polyphenol compounds can activate Nrf2 and inhibit MMP-9. Therefore, this review focuses on discussing Nrf2's role in oxidative stress and cataract formation, epigenetic effect in Nrf2 activity, and the association between Nrf2 and MMP-9 in cataract development. Moreover, we describe the protective role of flavonoids in cataract formation, targeting Nrf2 activation and MMP-9 synthesis inhibition as potential molecular targets in preventing cataracts.
白内障占全球失明人数的一半以上。白内障的形成主要是由于衰老以及氧化应激和炎症对眼睛晶状体的直接损伤。核因子-红细胞 2 相关因子 2（Nrf2）是细胞保护的转录因子，被称为氧化还原平衡的主要调节剂。Nrf2 调节近 600 个与细胞抵抗氧化应激因素有关的基因，包括衰老、疾病和炎症。据报道，Nrf2 破坏了激活核因子-κB（NFκB）和促炎细胞因子的氧化应激。这些细胞因子之一是基质金属蛋白酶 9（MMP-9），它参与晶状体上皮细胞（LEC）细胞外基质的分解，与白内障的发展有关。因此，在炎症过程中，MMP 的产生可能会被 Nrf2 途径或 Nrf2 抑制 NFκB 途径激活所减弱。此外，植物多酚由于其假定的安全性和功效、营养和抗氧化作用而受到关注。多酚化合物可以激活 Nrf2 并抑制 MMP-9。因此，本综述重点讨论了 Nrf2 在氧化应激和白内障形成中的作用、Nrf2 活性的表观遗传效应以及 Nrf2 与白内障形成中 MMP-9 的关系。此外，我们描述了类黄酮在白内障形成中的保护作用，靶向 Nrf2 激活和 MMP-9 合成抑制作为预防白内障的潜在分子靶点。
