Abstract
Background and Purpose. Diabetes mellitus (DM), hyperglycemia, and hypertension can result in diabetic retinopathy (DR), which is a major cause of blindness on a global scale. Development of DR is associated with decreased endothelial cells, increased basal membrane thickness, permeation of the retinal blood barrier, and neovascularization in patients. The purpose of the present review is to provide an overview of the findings regarding applications of phytochemicals for DR treatment and could be a beneficial resource for further clinical studies and also a basis for pharmaceutical purposes for drug design. Materials and Methods. A narrative literature review was performed from electronic databases including Web of Science, PubMed, and Scopus to analyze the effects of different phytochemicals to prevent or treat oxidation, angiogenesis, and inflammation in diabetic retinopathy. The inclusion criteria were original studies, which included the effects of different phytochemicals on diabetic retinopathy. The exclusion criteria included studies other than original articles, studies which assessed the effects of phytochemicals on nondiabetic retinopathy, and studies which used phytochemical-rich extracts. Results and Conclusions. Studies have shown that increased levels of inflammatory cytokines, angiogenic, and oxidative stress factors are involved in the progression and pathogenesis of DR. Therefore, phytochemicals with their anti-inflammatory, antiangiogenic, and antioxidant properties can prevent DR progression and retinal damage through various cellular mechanisms. It is also shown that some phytochemicals can simultaneously affect the inflammation, oxidation, and angiogenesis in DR.
Highlights
Diabetic retinopathy (DR) is one of the important microvascular complications of diabetes mellitus (DM), in which chronic hyperglycemia and hypertension affect the retinal microvasculature and cause critical damage leading to blindness worldwide [1–4]
Vascular endothelial growth factor (VEGF) is an angiogenic factor that is expressed in a large number of retinal cells exposed to hyperglycemia. is factor increases proliferation, migration, and tubal formation. erefore, in patients with DR, VEGF levels in the retina significantly increase, which is directly related to the progression of the disease [1, 9]
Genistein affects acute retinal pigment epithelial-19 cells (ARPE-19), cells treated with normal and high glucose were evaluated, and the results showed a significant reduction in VEGF levels and retinal angiogenesis [42]
Summary
Diabetic retinopathy (DR) is one of the important microvascular complications of diabetes mellitus (DM), in which chronic hyperglycemia and hypertension affect the retinal microvasculature and cause critical damage leading to blindness worldwide [1–4]. Vascular endothelial growth factor (VEGF) is an angiogenic factor that is expressed in a large number of retinal cells exposed to hyperglycemia. Erefore, in patients with DR, VEGF levels in the retina significantly increase, which is directly related to the progression of the disease [1, 9]. Chronic hyperglycemia in patients with DR causes high production of inflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin (IL1β), and subsequently destroys retinal cells [12]. In the inflammatory process of patients with DR, hyperglycemia increases the expression of nuclear factor kappa B (NF-κB), which causes many disorders, including increased retinal vascular leakage, leukocytosis, increased expression of inflammatory cytokines, and intercellular adhesion molecule (ICAM-1) [13, 14]. Studies have shown that phytochemicals can prevent DR progression through their antiangiogenic, antioxidant, and anti-inflammatory characteristics [7, 18, 19]. We intend to summarize an overview of the antiangiogenesis, anti-inflammatory, and antioxidant effects of phytochemicals on DR
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