Dataset Information

Identification of Novel Choroidal Neovascularization-Related Genes Using Laplacian Heat Diffusion Algorithm.

ABSTRACT: Choroidal neovascularization (CNV) is a type of eye disease that can cause vision loss. In recent years, many studies have attempted to investigate the major pathological processes and molecular pathogenic mechanisms of CNV. Because many diseases are related to genes, the genes associated with CNV need to be identified. In this study, we proposed a network-based approach for identifying novel CNV-associated genes. To execute such method, we first employed a protein-protein interaction network reported in STRING. Then, we applied a network diffusion algorithm, Laplacian heat diffusion, on this network by selecting validated CNV-related genes as the seed nodes. As a result, some novel genes that had unknown but strong relationships with validated genes were identified. Furthermore, we used a screening procedure to extract the most essential genes. Eleven latent CNV-related genes were finally obtained. Extensive analyses were performed to confirm that these genes are novel CNV-related genes.

SUBMITTER: Sheng M

PROVIDER: S-EPMC8440095 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Identification of Novel Choroidal Neovascularization-Related Genes Using Laplacian Heat Diffusion Algorithm.

Sheng Minjie M Cai Haiying H Cheng Ming M Li Jing J Zhang Jian J Liu Lihua L

BioMed research international 20210906

Choroidal neovascularization (CNV) is a type of eye disease that can cause vision loss. In recent years, many studies have attempted to investigate the major pathological processes and molecular pathogenic mechanisms of CNV. Because many diseases are related to genes, the genes associated with CNV need to be identified. In this study, we proposed a network-based approach for identifying novel CNV-associated genes. To execute such method, we first employed a protein-protein interaction network re ...[more]

PMID: 34532497

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Project description:Abnormal migration and proliferation of endothelial cells (EC) drive neovascular retinopathies. While anti-VEGF treatment slows progression, pathology is often supported by decrease in intraocular pigment epithelium-derived factor (PEDF), an endogenous inhibitor of angiogenesis. A surface helical 34-mer peptide of PEDF, comprising this activity, is efficacious in animal models of neovascular retina disease but remains impractically large for therapeutic use. We sought smaller fragments within this sequence that mitigate choroidal neovascularization (CNV). Expecting rapid intravitreal (IVT) clearance, we also developed a method to reversibly attach peptides to nano-carriers for extended delivery. Synthetic fragments of 34-mer yielded smaller anti-angiogenic peptides, and N-terminal capping with dicarboxylic acids did not diminish activity. Charge restoration via substitution of an internal aspartate by asparagine improved potency, achieving low nM apoptotic response in VEGF-activated EC. Two optimized peptides (PEDF 335, 8-mer and PEDF 336, 9-mer) were tested in a mouse model of laser-induced CNV. IVT injection of either peptide, 2-5 days before laser treatment, gave significant CNV decrease at day +14 post laser treatment. The 8-mer also decreased CNV, when administered as eye drops. Also examined was a nanoparticle-conjugate (NPC) prodrug of the 9-mer, having positive zeta potential, expected to display longer intraocular residence. This NPC showed extended efficacy, even when injected 14 days before laser treatment. Neither inflammatory cells nor other histopathologic abnormalities were seen in rabbit eyes harvested 14 days following IVT injection of PEDF 336 (>200 μg). No rabbit or mouse eye irritation was observed over 12-17 days of PEDF 335 eye drops (10 mM). Viability was unaffected in 3 retinal and 2 choroidal cell types by PEDF 335 up to 100 μM, PEDF 336 (100 μM) gave slight growth inhibition only in choroidal EC. A small anti-angiogenic PEDF epitope (G-Y-D-L-Y-R-V) was identified, variants (adipic-Sar-Y-N-L-Y-R-V) mitigate CNV, with clinical potential in treating neovascular retinopathy. Their shared active motif, Y - - - R, is found in laminin (Ln) peptide YIGSR, which binds Ln receptor 67LR, a known high-affinity ligand of PEDF 34-mer.

Dataset Information

Identification of Novel Choroidal Neovascularization-Related Genes Using Laplacian Heat Diffusion Algorithm.

Publications

Identification of Novel Choroidal Neovascularization-Related Genes Using Laplacian Heat Diffusion Algorithm.

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