@article {1446,
	title = {Hypoxic drive caused type 3 neovascularization in a preclinical model of exudative age-related macular degeneration.},
	journal = {Hum Mol Genet},
	volume = {28},
	year = {2019},
	month = {2019 10 15},
	pages = {3475-3485},
	abstract = {<p>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.</p>
},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddz159},
	author = {Zhang, Lijuan and Cui, Xuan and Han, Yangjun and Park, Karen Sophia and Gao, Xiaohong and Zhang, Ximei and Yuan, Zhigang and Hu, Yong and Hsu, Chun-Wei and Li, Xiaorong and Bassuk, Alexander G and Mahajan, Vinit B and Wang, Nan-Kai and Tsang, Stephen H}
}
