Pathogenic role of human C-reactive protein in diabetic retinopathy.

Abstract

PURPOSE:

Elevated blood levels of C-reactive protein (CRP) are associated with both type 1 and type 2 diabetes and diabetic complications, such as diabetic retinopathy (DR). However, its pathogenic role in DR remains unknown. The present study aims to investigate the potential role of CRP in DR pathogenesis and explore its underlying mechanism.

MATERIALS AND METHODS:

Human CRP transgenic (hCRP-Tg) rats were employed for streptozotocin (STZ)-induced diabetic and oxygen-induced retinopathy (OIR) models. The retina function was monitored by electroretinography (ERG) and retinal thickness was measured by optical coherence tomography (OCT). TUNEL and cell death ELISA were performed to measure the apoptosis. Oxidative stress was detected by the measurement of reactive oxygen species (ROS) in cells and 3-Nitrotyrosine staining in tissue sections.

RESULTS:

In non-diabetic condition, hCRP-Tg with elevated hCRP levels in the retinas demonstrated declined ERG responses and decreased retinal thickness. In STZ-induced diabetic condition, overexpression of hCRP deteriorated retinal neurodegeneration as shown by ERG and apoptosis assays. hCRP also exacerbated retinal leukostasis and acellular capillary formation induced by diabetes. In the OIR model, overexpression of hCRP exacerbated retinal neovascularization (NV). In retinal cell lines, hCRP treatment induced cell death and over-production of ROS. Furthermore, hCRP-induced overexpression of pro-inflammatory, pro-oxidative, and pro-angiogenic factors was associated with up-regulation of CD32 and the NF-κB signaling in the retinas.

CONCLUSIONS:

Elevated hCRP levels play a pathogenic role in DR. Targeting the hCRP-CD32-NF-κB pathway may represent a novel therapeutic strategy for DR.

• Authors: Fangfang Qiu, Xiang Ma, Young-Hwa Shin, Jianglei Chen, Qian Chen, Kelu Zhou, Wenjing Wu, Wentao Liang, Yalin Wu, Qing Song, Jian-Xing Ma
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 134 Issue 13 Pg. 1613-1629 (07 17 2020) ISSN: 1470-8736 [Electronic] England
• PMID: 32602547 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Reactive Oxygen Species
• Receptors, IgG
• C-Reactive Protein

Topics

• Animals
• Animals, Genetically Modified
• Apoptosis
• C-Reactive Protein (genetics, metabolism)
• Diabetic Retinopathy (complications, genetics, metabolism, pathology)
• Humans
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Receptors, IgG (genetics, metabolism)
• Retina (metabolism, pathology)
• Retinal Neovascularization (etiology, genetics, metabolism, pathology)
• Signal Transduction