title: The unfolded protein response in retinal vascular diseases: implications and therapeutic potential beyond protein folding.
abstract: Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness.
authors.affiliation: Department of Ophthalmology, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA; SUNY Eye Institute, Buffalo, NY, USA. Electronic address: xzhang38@buffalo.edu.
authors.forename: Sarah X
authors.initials: SX
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA; SUNY Eye Institute, Buffalo, NY, USA; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jacey H
authors.initials: JH
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA; SUNY Eye Institute, Buffalo, NY, USA.
authors.forename: Maulasri
authors.initials: M
authors.lastname: Bhatta
authors.affiliation: Department of Ophthalmology, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA; SUNY Eye Institute, Buffalo, NY, USA; Research Service, Veterans Administration Western New York Healthcare System, Buffalo, NY, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fliesler
authors.affiliation: Department of Ophthalmology, University at Buffalo, The State University of New York, Buffalo, NY, USA; Department of Biochemistry, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D005136:Eye Proteins / Q000502:physiology*; D006801:Humans; D012164:Retinal Diseases / Q000503:physiopathology*; D015861:Retinal Neovascularization / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D005136:Eye Proteins
keywords: Angiogenesis; Endoplasmic reticulum stress; Endothelial cells; Retina; Unfolded protein response; VEGF