PTEN对异染色质的保护在视网膜色素上皮细胞氧化损伤中的作用

视网膜色素上皮(RPE)的氧化损伤是导致年龄相关性黄斑变性（AMD）的主要原因。文献报道PTEN与RPE氧化损伤和AMD发生密切相关：PTEN活性在RPE氧化损伤中均显著下降；在小鼠RPE中敲除PTEN引起AMD病症。虽然PTEN对RPE结构和功能必不可少，但具体作用机制尚不明了。我们的最新发现揭示PTEN具有保护异染色质结构的重要功能。因为稳定的异染色质对抗氧化和延缓衰老起关键作用，推测PTEN可通过维持异染色质稳定在氧化应激中保护RPE细胞。 在本项目中，我们将利用前期建立的RPE细胞氧化损伤模型，确定PTEN对细胞活性的影响，并确定其稳定异染色质的功能在氧化应激中的作用。通过以上研究，我们将明确PTEN在RPE氧化损伤中的具体作用机制，期望为AMD治疗提供新的切入点。

Oxidative stress-induced retinal pigment epithelial (RPE) cell apoptosis is the major cause for age-related macular degeneration (AMD). It is known that the activity of PTEN dramatically decreased in RPE cells under oxidative stress. Furthermore, knockout of PTEN in mice RPE leads to AMD-like phenotype. Though PTEN is closely involved in RPE cell viability under oxidative stress and AMD, the exact function remains largely unknown. We recently found that PTEN maintains the heterochromatin stability. Since a stable heterochromatin structure plays a key role against oxidative stress and aging, we propose that PTEN promotes RPE cell survival under oxidative stress, and thus preventing AMD. In this study, we will use the previously established oxidative stress model, to determine the functions of PTEN in RPE cell survival, and to test if the protective function of PTEN in heterochromatin is involved. Our goal is to delineate the functions and exact mechanism that PTEN acts in resisting oxidative stress-induced RPE cell apoptosis, thus open new avenue for AMD treatment.