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Morphological characteristics of rat eye tissues observed by fundus fluorescein angiography (FFA) (×400) (n = 10). A. Control group; b. Diabetic retinopathy (DR) group; C. Anti-ACO3 group
Source publication
Background:
Diabetic retinopathy (DR) is one of the most common complications of diabetic microvascular disease and its pathogenesis is complicated. The PI3k/Akt signaling pathway plays an important role in the angiogenesis of DR.
Objectives:
To explore the molecular mechanisms of the ACO3 protein and related proteins in DR, in order to provide...
Contexts in source publication
Context 1
... FFA results showed that there was no significant DR and no abnormal phenomena in the control group (Fig. 1A). However, background fluorescence enhancement, vascular tortuosity and dilatation, and fluorescence leakage from neovascularization, intraretinal hemorrhage and microhemangioma were observed in the DR group (Fig. 1B). The characteristics of the eye tissue of the DR rats in the anti-ACO3 group were significantly better than in the DR ...
Context 2
... FFA results showed that there was no significant DR and no abnormal phenomena in the control group (Fig. 1A). However, background fluorescence enhancement, vascular tortuosity and dilatation, and fluorescence leakage from neovascularization, intraretinal hemorrhage and microhemangioma were observed in the DR group (Fig. 1B). The characteristics of the eye tissue of the DR rats in the anti-ACO3 group were significantly better than in the DR group, and the number of new microvessels was lower in the anti-ACO3 group (Fig. 1C). This indicates that the ACO3 protein is involved in regulating cell proliferation and inducing ...
Context 3
... and dilatation, and fluorescence leakage from neovascularization, intraretinal hemorrhage and microhemangioma were observed in the DR group (Fig. 1B). The characteristics of the eye tissue of the DR rats in the anti-ACO3 group were significantly better than in the DR group, and the number of new microvessels was lower in the anti-ACO3 group (Fig. 1C). This indicates that the ACO3 protein is involved in regulating cell proliferation and inducing ...
Citations
... PI3K/AKT signaling plays a key role in neovascularization in DR. Activation of PI3K/ AKT signaling by AGEs combined with RAGE may prolong endothelial cell survival, and cooperate with VEGF to promote retinal endothelial cell proliferation and migration, ultimately promoting neovascularization [30,31]. Activated AKT can mediate a variety of downstream target proteins, such as cell growth and proliferation through phosphorylation of mTOR, and apoptosis through inhibition of adverse expression [32,33]. ...
RAGE is a multiligand receptor for the immunoglobulin superfamily of cell surface molecules and is expressed in Müller cells, vascular endothelial cells, nerve cells and RPE cells of the retina. Diabetic retinopathy (DR) is a multifactorial disease associated with retinal inflammation and vascular abnormalities and is the leading cause of vision loss or impairment in older or working-age adults worldwide. Therapies aimed at reducing the inflammatory response and unnecessary angiogenesis can help slow the progression of DR, which in turn can save patients’ vision. To maximize the efficacy and minimize the side effects, treatments that target key players in the pathophysiological process of DR need to be developed. The interaction between RAGE and its ligands is involved in a variety of cytopathological alterations in the retina, including secretion of inflammatory factors, regulation of angiogenesis, oxidative stress, structural and functional changes, and neurodegeneration. In this review, we will summarize the pathologic pathways mediated by RAGE and its ligand interactions and discuss its role in the progression of diabetic retinopathy to explore potential therapeutic targets that are effective and safe for DR.
Objective:
Mingmu Dihuang Pill (MMDHP) is a traditional Chinese formula that has shown remarkable improvements of dry eyes, tearing, and blurry vision; however, the mechanisms underlying MMDHP treatment for diabetic retinopathy have not been fully understood. This study is aimed at identifying the molecular targets and active ingredients of MMDHP for the treatment of diabetic retinopathy based on network pharmacology.
Methods:
All active ingredients of MMDHP were retrieved from TCMSP and BATMAN-TCM databases, and the targets of active ingredients of MMDHP were predicted on the SwissTargetPrediction website. Diabetic retinopathy-related target sets were retrieved from GeneCards and OMIM databases, and the intersecting targets between targets of active ingredients of MMDHP and potential therapeutic targets of diabetic retinopathy were collected to generate the traditional Chinese medicine-ingredient-target-diabetic retinopathy network and to create the protein-protein interaction network. In addition, GO terms and KEGG pathway enrichment analyses were performed to identify the potential pathways, and molecular docking was employed to verify the binding of active ingredients of MMDHP to key targets of diabetic retinopathy.
Results:
Network pharmacology predicted 183 active ingredients and 904 targets from MMDHP, and 203 targets were intersected with the therapeutic targets of diabetic retinopathy. The top 10 hub targets included PIK3RA, TP53, SRC, JUN, HRAS, AKT1, VEGFA, EGFR, ESR1, and PI3KCA. GO terms and KEGG pathway enrichment analyses identified AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways as major pathways involved in MMDHP treatment for diabetic retinopathy. Molecular docking confirmed a good binding affinity of active ingredients of MMDHP, including luteolin, acacetin, naringenin, and alisol B, with AKT1, SRC, and VEGFA as the three key targets of diabetic retinopathy.
Conclusion:
MMDHP may be effective for the treatment of diabetic retinopathy through active ingredients luteolin, acacetin, naringenin, and alisol B via AKT1, SRC, and VEGFA in AGE-RAGE, PI3K-AKT, and Rap1 signaling pathways.
