Identifying mechanisms that detect and eliminate aneuploid cells

老年性黄斑变性、青光眼和白内障是视力的主要原因 失落和这三种疾病都与年龄有关。每一项都与积累有关 视网膜色素上皮、视网膜 神经节细胞、晶状体上皮细胞和小鼠模型研究表明 衰老细胞参与了这些眼病的发生和发展。 衰老细胞是在衰老过程中积累的异常细胞，不能分裂， 相反，会对组织功能产生破坏性影响。最近的研究表明， 衰老的细胞是非整倍体(有染色体异常)。非整倍体细胞 可以从发育中的组织中移除，初步数据表明其他 细胞根据不平衡的核糖体蛋白基因剂量识别它们。遗传 将对果蝇的眼睛进行筛查，以分离作用于 阻止正常细胞识别和消除非整倍体细胞。整体 将使用基因组测序和图谱方法来识别这些基因 受这些突变的影响，这将为深入了解分子 非整倍体细胞识别和去除的机制。预计这些 研究有助于理解衰老细胞是如何积累起来的，从而导致年龄相关 黄斑变性、青光眼和白内障，并建议减少 这些眼病的发病率和进展。

Age-related macular degeneration, glaucoma and cataract are major causes of vision loss and all three diseases are age-related. Each is associated with the accumulation of senescent cells in, respectively, the retinal pigmented epithelium, the retinal ganglion cells, and the lens epithelium, and mouse model studies indicate that senescent cells contribute to the occurrence and progression of these eye diseases. Senescent cells are abnormal cells that accumulate during aging, fail to divide and instead have disruptive effects on tissue function. Recent research indicates that senescent cells are aneuploid ie have chromosomal abnormalities. Aneuploid cells can be removed from developing tissues and preliminary data indicates that other cells recognize them based on imbalanced ribosomal protein gene dose. Genetic screens will be performed in fruitfly eyes to isolate gene mutations that act in normal cells to prevent their recognizing and eliminating aneuploid cells. Whole genome sequencing and mapping methods will be used to identify the genes affected by these mutations, which will provide insight into the molecular mechanisms of aneuploid cell recognition and removal. It is anticipated that these studies can help understand how senescent cells accumulate to cause age-related macular degeneration, glaucoma and cataract, and suggest approaches to reduce the incidence and progression of these eye disases.