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The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes.
Am J Pathol. 2020 05; 190(5):1080-1094.AJ

Abstract

This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy.

Authors+Show Affiliations

Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Ophthalmology and Visual Science, St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Clinical Research Center, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Division of Endocrinology & Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Division of Endocrinology & Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: jinah616@hanmail.net.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32354571

Citation

Chung, Yeon Woong, et al. "The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide On the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes." The American Journal of Pathology, vol. 190, no. 5, 2020, pp. 1080-1094.
Chung YW, Lee JH, Lee JY, et al. The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes. Am J Pathol. 2020;190(5):1080-1094.
Chung, Y. W., Lee, J. H., Lee, J. Y., Ju, H. H., Lee, Y. J., Jee, D. H., Ko, S. H., & A Choi, J. (2020). The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes. The American Journal of Pathology, 190(5), 1080-1094. https://doi.org/10.1016/j.ajpath.2020.01.011
Chung YW, et al. The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide On the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes. Am J Pathol. 2020;190(5):1080-1094. PubMed PMID: 32354571.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Anti-Inflammatory Effects of Glucagon-Like Peptide Receptor Agonist Lixisenatide on the Retinal Nuclear and Nerve Fiber Layers in an Animal Model of Early Type 2 Diabetes. AU - Chung,Yeon Woong, AU - Lee,Jae Hyung, AU - Lee,Ji Young, AU - Ju,Hyun Hee, AU - Lee,Ye-Jee, AU - Jee,Dong Hyun, AU - Ko,Seung-Hyun, AU - A Choi,Jin, Y1 - 2020/04/27/ PY - 2019/07/27/received PY - 2020/01/11/revised PY - 2020/01/17/accepted PY - 2020/5/2/pubmed PY - 2020/6/23/medline PY - 2020/5/2/entrez SP - 1080 EP - 1094 JF - The American journal of pathology JO - Am. J. Pathol. VL - 190 IS - 5 N2 - This study explored the anti-inflammatory effects of a glucagon-like peptide-1 receptor agonist (GLP-1RA), known as lixisenatide, on the eyes of early type 2 diabetic mice. Diabetic (db/db) mice were divided into three groups: GLP-1RA [lixisenatide (LIX)], insulin (INS) with controlled hyperglycemia based on the glucose concentration of lixisenatide, and diabetic control (D-CON). Nondiabetic control mice (db/dm) were also characterized for comparison. After 8 weeks of treatment, mRNA levels of inflammatory markers, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, immunohistochemical staining; Western blot of glial fibrillary acidic protein (GFAP) and thioredoxin-interacting protein; and retinal thickness were assessed in the central and peripheral neurosensory retina. LIX showed decreased immunohistochemical staining for both thioredoxin-interacting protein and GFAP in the central and peripheral neurosensory retina compared with D-CON and INS, and decreased expression of these proteins in the neurosensory retina and immunohistochemical staining in the optic nerve head for GFAP compared with D-CON. The inner nuclear layer in the peripheral retina in LIX was only thinner than those of D-CON and INS. In an early type 2 diabetic mouse model, lixisenatide treatment showed superior anti-inflammatory effects on the retina and optic nerve head independent of hyperglycemia. Thus, the neuroprotective effects of lixisenatide treatment in the peripheral inner nuclear layer should be evaluated in early type 2 diabetic retinopathy. SN - 1525-2191 UR - https://www.unboundmedicine.com/medline/citation/32354571/The_Anti-Inflammatory_Effects_of_Glucagon-Like_Peptide_Receptor_Agonist_Lixisenatide_on_the_Retinal_Nuclear_and_Nerve_Fiber_Layers_in_an_Animal_Model_of_Early_Type_2_Diabetes L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(20)30089-4 DB - PRIME DP - Unbound Medicine ER -