| 1 | Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy显示文摘Diabetic retinopathy(DR)affects approximately one-third of diabetic patients and,if left untreated,progresses to proliferative DR(PDR)with associated vitreous hemorrhage,retinal detachment,iris neovascularization,glaucoma and irreversible blindness.In vitreous samples of human patients with PDR,we found elevated levels of hypoxia inducible factor 1 alpha(HIF1α).HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases.To recreate the human PDR phenotype for a preclinical animal model,we generated a mouse with neuroretinal-specific loss of the von Hippel Lindau tumor suppressor protein,a protein that targets HIF1αfor ubiquitination.We found that the neuroretinal cells in these mice overexpressed HIF1αand developed severe,irreversible ischemic retinopathy that has features of human PDR.Rapid progression of retinopathy in these mutant mice should facilitate the evaluation of therapeutic agents for ischemic and inflammatory blinding disorders.In addition,this model system can be used to manipulate the modulation of the hypoxia signaling pathways,for the treatment of non-ocular ischemic and inflammatory disorders. | Katherine J Wert Vinit B Mahajan Lijuan Zhang Yuanqing Yan Yao Li Joaquin Tosi Chun Wei Hsu Takayuki Nagasaki Kerstin M Janisch Maria B Grant MaryAnn Mahajan Alexander G Bassuk Stephen H Tsang | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 1 |
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