| Literature DB >> 31518400 |
Lijuan Zhang1, Xuan Cui2,3,4, Yangjun Han5, Karen Sophia Park3,4, Xiaohong Gao1, Ximei Zhang1, Zhigang Yuan1, Yong Hu6, Chun-Wei Hsu3,4, Xiaorong Li2, Alexander G Bassuk7, Vinit B Mahajan8,9, Nan-Kai Wang3,4, Stephen H Tsang3,4,10.
Abstract
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.Entities:
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Year: 2019 PMID： 31518400 PMCID： PMC7275777 DOI： 10.1093/hmg/ddz159
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150