Deoye Tonade1, Haitao Liu2, Krzysztof Palczewski1, Timothy S Kern3,4,5. 1. Department of Pharmacology, W309 Wood Building, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USA. 2. Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. 3. Department of Pharmacology, W309 Wood Building, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USA. tsk@case.edu. 4. Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. tsk@case.edu. 5. Veterans Administration Medical Center Research Service, Cleveland, OH, USA. tsk@case.edu.
Abstract
AIMS/HYPOTHESIS: Recent studies suggest that photoreceptor cells produce mediators or products that contribute to retinal capillary damage in diabetes. The purpose of this study was to determine if photoreceptor cells release soluble factors that contribute to retinal vascular permeability in diabetes. METHODS: To assess retinal vascular leakage, a streptozotocin-induced mouse model of diabetes, with hyperglycaemia for 8 months, and age-matched control mice, were injected with FITC-BSA. Fluorescence microscopy was used to detect leakage of FITC-BSA from the retinal vasculature into the neural retina. Ex vivo and in vitro experiments were performed to determine if photoreceptor cells released products that directly increased retinal endothelial cell permeability or cell death. Effects of products released by photoreceptors on tight junction and cell adhesion proteins were assessed by quantitative reverse transcription PCR (qRT-PCR). Inflammatory products released by photoreceptors into media were measured using protein arrays. RESULTS: Eight months duration of diabetes increased retinal vascular permeability in wild-type mice, but this defect was inhibited in opsin-deficient diabetic mice in which photoreceptor cells had degenerated earlier. Photoreceptor cells from diabetic wild-type mice released inflammatory products (e.g. IL-1α, IL-1β, IL-6, IL-12, chemokine C-X-C motif ligand 1 [CXCL1], monocyte chemoattractant protein 1 [MCP-1], CXCL12a, I-309, chemokine ligand 25 [CCL25] and TNF-α), which directly contributed to increased retinal endothelial cell permeability, at least in part via changes in claudin (tight junction) mRNA. Products released from photoreceptor cells from diabetic mice or under diabetes-like conditions did not directly kill retinal endothelial cells in vitro. CONCLUSIONS/ INTERPRETATION: Photoreceptor cells can produce inflammatory products that contribute to retinal vascular permeability in mouse models of diabetes.
AIMS/HYPOTHESIS: Recent studies suggest that photoreceptor cells produce mediators or products that contribute to retinal capillary damage in diabetes. The purpose of this study was to determine if photoreceptor cells release soluble factors that contribute to retinal vascular permeability in diabetes. METHODS: To assess retinal vascular leakage, a streptozotocin-induced mouse model of diabetes, with hyperglycaemia for 8 months, and age-matched control mice, were injected with FITC-BSA. Fluorescence microscopy was used to detect leakage of FITC-BSA from the retinal vasculature into the neural retina. Ex vivo and in vitro experiments were performed to determine if photoreceptor cells released products that directly increased retinal endothelial cell permeability or cell death. Effects of products released by photoreceptors on tight junction and cell adhesion proteins were assessed by quantitative reverse transcription PCR (qRT-PCR). Inflammatory products released by photoreceptors into media were measured using protein arrays. RESULTS: Eight months duration of diabetes increased retinal vascular permeability in wild-type mice, but this defect was inhibited in opsin-deficient diabeticmice in which photoreceptor cells had degenerated earlier. Photoreceptor cells from diabetic wild-type mice released inflammatory products (e.g. IL-1α, IL-1β, IL-6, IL-12, chemokine C-X-C motif ligand 1 [CXCL1], monocyte chemoattractant protein 1 [MCP-1], CXCL12a, I-309, chemokine ligand 25 [CCL25] and TNF-α), which directly contributed to increased retinal endothelial cell permeability, at least in part via changes in claudin (tight junction) mRNA. Products released from photoreceptor cells from diabeticmice or under diabetes-like conditions did not directly kill retinal endothelial cells in vitro. CONCLUSIONS/ INTERPRETATION: Photoreceptor cells can produce inflammatory products that contribute to retinal vascular permeability in mouse models of diabetes.
Authors: Yunpeng Du; Megan Cramer; Chieh Allen Lee; Jie Tang; Arivalagan Muthusamy; David A Antonetti; Hui Jin; Krzysztof Palczewski; Timothy S Kern Journal: FASEB J Date: 2015-02-09 Impact factor: 5.191
Authors: Tanyth E de Gooyer; Kathryn A Stevenson; Pete Humphries; David A C Simpson; Timothy M Curtis; Tom A Gardiner; Alan W Stitt Journal: Invest Ophthalmol Vis Sci Date: 2006-12 Impact factor: 4.799
Authors: Markus Puhlmann; David M Weinreich; Jeffrey M Farma; Nancy M Carroll; Ewa M Turner; H Richard Alexander Journal: J Transl Med Date: 2005-09-30 Impact factor: 5.531
Authors: Haitao Liu; Jie Tang; Yunpeng Du; Aicha Saadane; Deoye Tonade; Ivy Samuels; Alex Veenstra; Krzysztof Palczewski; Timothy S Kern Journal: Invest Ophthalmol Vis Sci Date: 2016-08-01 Impact factor: 4.799
Authors: Sarah I Lindstrom; Sigrun Sigurdardottir; Thomas E Zapadka; Jie Tang; Haitao Liu; Brooklyn E Taylor; Dawn G Smith; Chieh A Lee; John DeAngelis; Timothy S Kern; Patricia R Taylor Journal: J Diabetes Complications Date: 2019-05-29 Impact factor: 2.852
Authors: Haitao Liu; Emma M Lessieur; Aicha Saadane; Sarah I Lindstrom; Patricia R Taylor; Timothy S Kern Journal: Diabetologia Date: 2019-10-14 Impact factor: 10.122
Authors: Sigrun Sigurdardottir; Thomas E Zapadka; Sarah I Lindstrom; Haitao Liu; Brooklyn E Taylor; Chieh A Lee; Timothy S Kern; Patricia R Taylor Journal: Cell Immunol Date: 2019-05-02 Impact factor: 4.868
Authors: Nicholas C Holoman; Jacob J Aiello; Timothy D Trobenter; Matthew J Tarchick; Michael R Kozlowski; Emily R Makowski; Darryl C De Vivo; Charandeep Singh; Jonathan E Sears; Ivy S Samuels Journal: J Neurosci Date: 2021-02-23 Impact factor: 6.167