自噬对眼睛的分化和功能有重要的作用。RanGAP1是核孔复合物的重要组成成分，在核质转运中发挥重要的功能，同时SUMO-ranGAP1会与ranBP2和UBC9在核孔胞质侧形成一个多亚基E3 SUMO连接酶。我们在前期的工作中发现，ranGAP1在小鼠眼分化期高表达，在成熟小鼠的晶状体上皮和视网膜中高表达，在细胞中干扰ranGAP1后自噬的激活受到抑制，过表达ranGAP1后自噬的激活得到促进，而未被SUMO化修饰的ranGAP1不具备这项功能。上述结果提示SUMO-ranGAP1通过调节自噬参与晶状体和视网膜的发育和功能。本课题将在前期工作的基础上，阐明：1）ranGAP1在眼睛中调节自噬的分子机制；2）SUMO化修饰在眼睛中调节自噬的分子机制；3）ranGAP1在晶状体和视网膜中的功能。这些结果将进一步阐明自噬调节的分子机制，揭示ranGAP1调节自噬在晶状体和视网膜中的重要功能。

Autophagy in an important cellular mechanism for the intracellular quality control. It plays a critical role during eye development, and maintenance of cellular function and homeostasis. RanGAP1 is a component of the nuclear pore complex and a key regulator of the nucleocytoplasmic transport. At its functional status, RanGAP1 is sumoylated and forms a complex with RanBP2 and UBC9 at the cytoplasmic face of the nuclear pore, exerting E3 ligase activity. Our previous studies reveal that RanGAP1 is highly expressed during mouse eye development and in the adult ocular tissue including both lens epithelial cells and retina. Silencing RanGAP1 in αNT4-1 and ARPE-19 inhibits autophagy activity while overexpression of RanGAP1 promotes autophagy induced by serum starvation. The autophagy activists of RanGAP1 is relied on its sumoylation. These observations promote us to hypothesis that sumoylated RanGAP1 is involved in the development and functional maintenance of both lens and retina. To validate the hypothesis, we prepare to 1) Elucidate the molecular mechanism mediating RanGAP1 control autophagy in the eye, 2) Determine the molecular mechanism mediating sumoylation control of autophagy in the eye, 3) Demonstrate the functional mechanism of sumoylated RanGAP1-controlled autophagy in major ocular diseases including cataract formation and retina degeneration. These results will provide novel information regarding the molecular mechanism mediating autophagy control, and demonstrate the functions of RanGAP1-controlled autophagy in both lens and retina.