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.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Zhang L,Cui X,Han Y,Park KS,Gao X,Zhang X,Yuan Z,Hu Y,Hsu CW,Li X,Bassuk AG,Mahajan VB,Wang NK,Tsang SHdoi
10.1093/hmg/ddz159subject
Has Abstractpub_date
2019-10-15 00:00:00pages
3475-3485issue
20eissn
0964-6906issn
1460-2083pii
5568676journal_volume
28pub_type
杂志文章abstract::Targeting of numerous transmembrane proteins to the cell surface is thought to depend on their recognition by cargo receptors that interact with the adaptor machinery for anterograde traffic at the distal end of the Golgi complex. We report here on consortin, a novel integral membrane protein that is predicted to be i...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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更新日期:2007-10-15 00:00:00
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journal_title:Human molecular genetics
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更新日期:2018-05-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.12.2151
更新日期:1997-11-01 00:00:00
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journal_title:Human molecular genetics
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