|Title||Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Zhang, Lijuan, Cui Xuan, Han Yangjun, Park Karen Sophia, Gao Xiaohong, Zhang Ximei, Yuan Zhigang, Hu Yong, Hsu Chun-Wei, Li Xiaorong, Bassuk Alexander G., Mahajan Vinit B., Wang Nan-Kai, and Tsang Stephen H.|
|Journal||Hum Mol Genet|
|Date Published||2019 10 15|
Hypoxia associated with the high metabolic demand of rods has been implicated in the pathology of age-related macular degeneration (AMD), the most common cause of adult blindness in the developed world. The majority of AMD-associated severe vision loss cases are due to exudative AMD, characterized by neovascularization. To further investigate the causes and histopathology of exudative AMD, we conditionally induced hypoxia in a novel preclinical AMD model (Pde6gcreERT2/+;Vhl-/-) by targeting Vhl and used multimodal imaging and immunohistochemistry to track the development of hypoxia-induced neovascularization. In addition to developing a preclinical model that phenocopies exudative AMD, our studies revealed that the photoreceptor hypoxic response initiates and drives type 3 neovascularization, mainly in the outer retina. Activation of the VHL-HIF1a-VEGF-EPO pathway in the adult retina led to long-term neovascularization, retinal hemorrhages and compromised retinal layers. Our novel preclinical model would accelerate the testing of therapies that use metabolomic approaches to ameliorate AMD.
|Alternate Journal||Hum. Mol. Genet.|