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Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy.

ABSTRACT: The increased incidence of diabetic retinopathy (DR) and the legacy effect associated with it has raised a great concern toward the need to find early diagnostic and treatment strategies. Identifying alterations in genes and microRNAs (miRNAs) is one of the most critical steps toward understanding the mechanisms by which a disease progresses, and this can be further used in finding potential diagnostic and prognostic biomarkers and treatment methods. We selected different datasets to identify altered genes and miRNAs. The integrative analysis was employed to find potential candidate genes (differentially expressed and aberrantly methylated genes that are also the target of altered miRNAs) and early genes (genes showing altered expression and methylation pattern during early stage of DR) for DR. We constructed a protein-protein interaction (PPI) network to find hub genes (potential candidate genes showing a greater number of interactions) and modules. Gene ontologies and pathways associated with the identified genes were analyzed to determine their role in DR progression. A total of 271 upregulated-hypomethylated genes, 84 downregulated-hypermethylated genes, 11 upregulated miRNA, and 30 downregulated miRNA specific to DR were identified. 40 potential candidate genes and 9 early genes were also identified. PPI network analysis revealed 7 hub genes (number of interactions >5) and 1 module (score = 5.67). Gene ontology and pathway analysis predicted enrichment of genes in oxidoreductase activity, binding to extracellular matrix, immune responses, leukocyte migration, cell adhesion, PI3K-Akt signaling pathway, ECM receptor interaction, etc., and thus their association with DR pathogenesis. In conclusion, we identified 7 hub genes and 9 early genes that could act as a potential prognostic, diagnostic, or therapeutic target for DR, and a few early genes could also play a role in metabolic memory phenomena.

SUBMITTER: Kumari N

PROVIDER: S-EPMC7693709 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy.

Kumari Nidhi N Karmakar Aditi A Chakrabarti Saikat S Ganesan Senthil Kumar SK

Frontiers in genetics 20201112

The increased incidence of diabetic retinopathy (DR) and the legacy effect associated with it has raised a great concern toward the need to find early diagnostic and treatment strategies. Identifying alterations in genes and microRNAs (miRNAs) is one of the most critical steps toward understanding the mechanisms by which a disease progresses, and this can be further used in finding potential diagnostic and prognostic biomarkers and treatment methods. We selected different datasets to identify al ...[more]

PMID: 33304382

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Project description:PurposeTo assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus.MethodsAn adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors.ResultsTen healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes.ConclusionsThe extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

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Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy.

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Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy.

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