Expression of Osteopontin and Integrin αvβ3 Receptor in Retina of Diabetic Guinea Pigs with High Myopia

Abstract

Introduction: The study aimed to investigate the effect of high myopia on the expression of retinal osteopontin (OPN) and integrin αvβ3 receptor in guinea pigs and determine the relationship between high myopia and diabetic retinopathy (DR). Methods: Ninety-three-week-old male guinea pigs were randomly divided into four groups that included normal control group (NOR, n = 18), high myopia group (HM, n = 24), diabetes group (DR, n = 24), and diabetes with high myopia group (DR+HM, n = 24). HM was induced by form deprivation (FDHM) in the right eye. The DR group was injected with 5% streptozotocin 280 mg/kg intraperitoneally in the lower left abdomen of guinea pigs. The DRHM group was subjected to the same treatment as the HM and DR groups. Eighteen guinea pigs in each group were randomly selected to complete the experimental measurement. After enucleation of eyeballs, HE and immunohistochemical staining were performed to observe the retina morphology and count the positive rate of OPN and integrin αvβ3 receptor. Results: Diabetic retinal changes were found in group DR and HM+DR. The degree of retinal change in group HM+DR was less than that in group DR. In the DR group, the morphology of retinal tissue was loose, the number of cells decreased, retinal microaneurysms were increased, and a small amount of small artery embolism and venous thrombosis were observed. Although the retinal structure in the HM+DR group also became thinner, looser, and disordered, only a small number of microaneurysms were observed compared with the diabetic group. Immunohistochemical staining showed that the expression of OPN and integrin αvβ3 receptors in the diabetic groups (DR, HM+DR) was significantly higher than in the HM and NOR groups. The positive expression rates of OPN and integrin αvβ3 receptors in group HM+DR were significantly lower than those in group DR (p < 0.05). Conclusion: The expression of OPN and integrin αvβ3 receptor in the retina of diabetic guinea pigs with high myopia was lower than that of diabetic models, which may be due to the influence of high myopia on neovascularization in DR.

© 2022 The Author(s). Published by S. Karger AG, Basel

References Jiang JJ, Li XX, Yuan L, Ji LN, Wu X. [Ocular biological structures and relevant risk factors in the occurrence of diabetic retinopathy in diabetes mellitus patients]. Zhonghua Yan Ke Za Zhi. 2012 Oct;48(10):898–902. Lim LS, Lamoureux E, Saw SM, Tay WT, Mitchell P, Wong TY. Are myopic eyes less likely to have diabetic retinopathy? Ophthalmology. 2010 Mar;117(3):524–30. Man REK, Sasongko MB, Wang JJ, Lamoureux EL. Association between myopia and diabetic retinopathy: a review of observational findings and potential mechanisms. Clin Exp Ophthalmol. 2013 Apr;41(3):293–301. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010 Jan;10(1):9–22. Brooks PC, Clark RAF, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569–71. Fu Y, Ponce ML, Thill M, Yuan P, Wang NS, Csaky KG. Angiogenesis inhibition and choroidal neovascularization suppression by sustained delivery of an integrin antagonist, EMD478761. Invest Ophthalmol Vis Sci. 2007 Nov;48(11):5184–90. Bhatwadekar AD, Kansara V, Luo Q, Ciulla T. Anti-integrin therapy for retinovascular diseases. Expert Opin Investig Drugs. 2020 Sep;29(9):935–45. Kahles F, Findeisen HM, Bruemmer D. Osteopontin: a novel regulator at the cross roads of inflammation, obesity and diabetes. Mol Metab. 2014 Jul;3(4):384–93. Huang Q, Sheibani N. High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. Am J Physiol Cell Physiol. 2008 Dec;295(6):C1647–57. Zhang X, Chee WK, Liu S, Tavintharan S, Sum CF, Lim SC, et al. Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes. Mol Vis. 2018;24:165–73. Takagi H, Suzuma K, Otani A, Oh H, Koyama S, Ohashi H, et al. Role of vitronectin receptor-type integrins and osteopontin in ischemia-induced retinal neovascularization. Jpn J Ophthalmol. 2002 May-Jun;46(3):270–8. Kase S, Yokoi M, Saito W, Furudate N, Ohgami K, Kitamura M, et al. Increased osteopontin levels in the vitreous of patients with diabetic retinopathy. Ophthalmic Res. 2007;39(3):143–7. Denhardt DT, Chambers AF. Overcoming obstacles to metastasis--defenses against host defenses: osteopontin (OPN) as a shield against attack by cytotoxic host cells. J Cell Biochem. 1994 Sep;56(1):48–51. Standal T, Borset M, Sundan A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol. 2004 Sep;26(3):179–84. Dai J, Peng L, Fan K, Wang H, Wei R, Ji G, et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene. 2009 Sep 24;28(38):3412–22. Shijubo N, Uede T, Kon S, Nagata M, Abe S. Vascular endothelial growth factor and osteopontin in tumor biology. Crit Rev Oncog. 2000;11(2):135–46. Al Kahtani E, Xu Z, Al Rashaed S, Wu L, Mahale A, Tian J, et al. Vitreous levels of placental growth factor correlate with activity of proliferative diabetic retinopathy and are not influenced by bevacizumab treatment. Eye. 2017 Apr;31(4):529–36. Ahuja S, Saxena S, Akduman L, Meyer CH, Kruzliak P, Khanna VK. Serum vascular endothelial growth factor is a biomolecular biomarker of severity of diabetic retinopathy. Int J Retina Vitreous. 2019;5:29. Ang WJ, Zunaina E, Norfadzillah AJ, Raja-Norliza RO, Julieana M, Ab-Hamid SA, et al. Evaluation of vascular endothelial growth factor levels in tears and serum among diabetic patients. PLoS One. 2019;14(8):e0221481. Wang X, Tang L, Gao L, Yang Y, Cao D, Li Y. Myopia and diabetic retinopathy: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2016 Jan;111:1–9. Lin Z, Li D, Zhai G, Wang Y, Wen L, Ding XX, et al. High myopia is protective against diabetic retinopathy via thinning retinal vein: A report from Fushun Diabetic Retinopathy Cohort Study (FS-DIRECT). Diab Vasc Dis Res. 2020 Jul-Aug;17(4):1479164120940988. Man REK, Lamoureux EL, Taouk Y, Xie J, Sasongko MB, Best WJ, et al. Axial length, retinal function, and oxygen consumption: a potential mechanism for a lower risk of diabetic retinopathy in longer eyes. Invest Ophthalmol Vis Sci. 2013 Nov 19;54(12):7691–8. Sawada O, Kawamura H, Kakinoki M, Sawada T, Ohji M. Vascular endothelial growth factor in the aqueous humour in eyes with myopic choroidal neovascularization. Acta Ophthalmol. 2011 Aug;89(5):459–62. Ganesan S, Raman R, Reddy S, Krishnan T, Kulothungan V, Sharma T. Prevalence of myopia and its association with diabetic retinopathy in subjects with type II diabetes mellitus: a population-based study. Oman J Ophthalmol. 2012 May;5(2):91–6. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: May 29, 2022
Accepted: July 22, 2022
Published online: August 29, 2022

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 2

ISSN: 0030-3747 (Print)
eISSN: 1423-0259 (Online)

For additional information: https://www.karger.com/ORE

Figures Thumbnail Thumbnail Thumbnail Tables Thumbnail Thumbnail

留言 (0)

沒有登入
gif