title: The unfolded protein response and diabetic retinopathy.
abstract: Diabetic retinopathy, a common complication of diabetes, is the leading cause of blindness in adults. Diabetes chronically damages retinal blood vessels and neurons likely through multiple pathogenic pathways such as oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. To relieve ER stress, the cell activates an adaptive mechanism known as the unfolded protein response (UPR). The UPR coordinates the processes of protein synthesis, protein folding, and degradation to ensure proteostasis, which is vital for cell survival and activity. Emerging evidence suggests that diabetes can activate all three UPR branches in retinal cells, among which the PERK/ATF4 pathway is the most extensively studied in the development of diabetic retinopathy. X-box binding protein 1 (XBP1) is a major transcription factor in the core UPR pathway and also regulates a variety of genes involved in cellular metabolism, redox state, autophagy, inflammation, cell survival, and vascular function. The exact function and implication of XBP1 in the pathogenesis of diabetic retinopathy remain elusive. Focusing on this less studied pathway, we summarize recent progress in studies of the UPR pertaining to diabetic changes in retinal vasculature and neurons, highlighting the perspective of XBP1 as a potential therapeutic target in diabetic retinopathy.
authors.affiliation: Departments of Ophthalmology and Biochemistry (Ira G. Ross Eye Institute), School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 308 Farber Hall, Buffalo, NY 14214, USA ; SUNY Eye Institute, Buffalo, NY 14214, USA ; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Jacey Hongjie
authors.identifier: 0000-0003-1729-5282
authors.initials: JH
authors.lastname: Ma
authors.affiliation: Departments of Ophthalmology and Biochemistry (Ira G. Ross Eye Institute), School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 308 Farber Hall, Buffalo, NY 14214, USA ; SUNY Eye Institute, Buffalo, NY 14214, USA.
authors.forename: Josh J
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Departments of Ophthalmology and Biochemistry (Ira G. Ross Eye Institute), School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, 308 Farber Hall, Buffalo, NY 14214, USA ; SUNY Eye Institute, Buffalo, NY 14214, USA.
authors.forename: Sarah X
authors.initials: SX
authors.lastname: Zhang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001343:Autophagy; D004268:DNA-Binding Proteins / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic; D000071701:Regulatory Factor X Transcription Factors; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response / Q000187:drug effects; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051701:Activating Transcription Factor 4; D000893:Anti-Inflammatory Agents; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D019892:eIF-2 Kinase; C497109:ATF4 protein, human; C000605543:XBP1 protein, human; C460640:EIF2AK3 protein, human