Journal article
Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy
Signal transduction and targeted therapy, Vol.1(1), p.16005
2016
DOI: 10.1038/sigtrans.2016.5
PMCID: PMC4868361
PMID: 27195131
Abstract
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 HIF1α for ubiquitination. We found that the neuroretinal cells in these mice overexpressed HIF1α and 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.
Details
- Title: Subtitle
- Neuroretinal hypoxic signaling in a new preclinical murine model for proliferative diabetic retinopathy
- Creators
- Katherine J Wert - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USA; Institute of Human Nutrition, Columbia University, New York, NY, USAVinit B Mahajan - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA; Omics Laboratory, University of Iowa, Iowa City, IA, USALijuan Zhang - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USAYuanqing Yan - Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USAYao Li - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USAJoaquin Tosi - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USAChun Wei Hsu - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USATakayuki Nagasaki - Edward S. Harkness Eye Institute, Columbia University, New York, NY, USAKerstin M Janisch - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USAMaria B Grant - Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USAMaryAnn Mahajan - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA; Omics Laboratory, University of Iowa, Iowa City, IA, USAAlexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, IA, USAStephen H Tsang - Bernard and Shirlee Brown Glaucoma Laboratory and Barbara & Donald Jonas Laboratory of Regenerative Medicine, Columbia University, New York, NY, USA; Edward S. Harkness Eye Institute, Columbia University, New York, NY, USA; Institute of Human Nutrition, Columbia University, New York, NY, USA; New York Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA; Department of Pathology and Cellular Biology, Columbia University, New York, NY, USA
- Resource Type
- Journal article
- Publication Details
- Signal transduction and targeted therapy, Vol.1(1), p.16005
- DOI
- 10.1038/sigtrans.2016.5
- PMID
- 27195131
- PMCID
- PMC4868361
- NLM abbreviation
- Signal Transduct Target Ther
- ISSN
- 2095-9907
- eISSN
- 2059-3635
- Publisher
- England
- Grant note
- R01 EY018213 / NEI NIH HHS R01 DK090730 / NIDDK NIH HHS R01 EY026682 / NEI NIH HHS T32 DK007647 / NIDDK NIH HHS F32 CA196065 / NCI NIH HHS R01 EY012601 / NEI NIH HHS R01 EY025225 / NEI NIH HHS T32 EY013933 / NEI NIH HHS R01 EY016822 / NEI NIH HHS P30 CA013696 / NCI NIH HHS R01 EY024698 / NEI NIH HHS R01 EY007739 / NEI NIH HHS K08 EY020530 / NEI NIH HHS R01 HL110170 / NHLBI NIH HHS P30 EY019007 / NEI NIH HHS
- Language
- English
- Date published
- 2016
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984020619702771
Metrics
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