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Identification of lncRNAs involved in biological regulation in early age-related macular degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs) in the development and progression of early AMD is unclear.We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs.The expression profiles of 9 cases of AMD and 7 controls were studied. A total of 266 differentially expressed genes (DEGs) were detected (94 upregulated and 172 downregulated). Among all the DEGs, 64 were lncRNAs. Advanced bioinformatics analyses demonstrated that differentially expressed lncRNAs could play significant roles in visual perception, sensory perception of light stimulus, and cognition. The pathway analyses showed that the two most significantly influenced Kyoto Encyclopedia of Genes and Genomes pathways were those of phototransduction and purine metabolism. By the analyses of the key lncRNAs, it was found that RP11-234O6.2 was downregulated in the aging retinal pigment epithelium (RPE) cellular model. Exogenous RP11-234O6.2 treatment led to increased cell viability and improved apoptosis but it did not affect the cell migration ability of aging RPE cells.This study indicated that lncRNAs are differentially expressed in early AMD and may produce important regulative effects. An lncRNA, RP11-234O6.2, might be involved in the biological regulation of early AMD and have therapeutic potential.

SUBMITTER: Zhu W

PROVIDER: S-EPMC5655033 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Identification of lncRNAs involved in biological regulation in early age-related macular degeneration.

Zhu Wei W Meng Yi-Fang YF Xing Qian Q Tao Jian-Jun JJ Lu Jiong J Wu Yan Y

International journal of nanomedicine 20171017

<h4>Background</h4>Age-related macular degeneration (AMD) is one of the most common causes of adult blindness in developed countries. However, the role of long noncoding RNAs (lncRNAs) in the development and progression of early AMD is unclear.<h4>Methods</h4>We established the lncRNA profile of early AMD by reannotation of microarrays from the gene expression omnibus database. Quantitative real-time polymerase chain reaction was used to determine the expression of selected lncRNAs.<h4>Results</ ...[more]

PMID: 29089757

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Project description:Loss of choriocapillaris (CC) in advanced age-related macular degeneration (AMD) is well documented but changes in early AMD have not been quantified. Postmortem eyes from donors with clinically documented early AMD were examined in choroidal whole mounts to determine the area, pattern, and severity of CC loss. Choroids from postmortem human eyes without AMD (n = 7; mean age = 86.1) and from eyes with a Grade 2 clinical classification of early AMD (n = 7; mean age = 87) were immunolabeled with Ulex europaeus agglutinin (UEA) lectin-FITC to stain blood vessels. Whole mounts were imaged using confocal microscopy and image analysis was performed to determine the area of vascular changes and density of vasculature (percent vascular area, %VA). All areas evaluated had a complete RPE monolayer upon gross examination. In age-matched control eyes, the CC had broad lumens and a homogenous pattern of freely interconnecting capillaries. The mean %VA ± standard deviation in submacula of control subjects was 78.1 ± 3.25%. In eyes with early AMD, there was a significant decrease in mean %VA to 60.1 ± 10.4% (p < 0.0001). The paramacular %VA was not significantly different in eyes with or without AMD. The area of submacular choroid affected by CC dropout was 0.04 ± 0.09 mm2 in control eyes. In eyes with early AMD, the mean area affected by CC dropout was significantly increased (10.4 ± 6.1 mm2; p < 0.001). In some cases, incipient neovascular buds were observed at the border of regions with CC dropout in early AMD choroids. In conclusion, UEA lectin-labeled choroidal whole mounts from donors with clinically documented early AMD has provided a unique opportunity to examine regional changes in vascular pathology associated with choriocapillaris. The study demonstrated attenuation of submacular CC in early AMD subjects but no vascular pathology was observed outside the submacular region. While the affected area in some eyes was quite extensive histologically, these changes may not be detectable clinically using standard in vivo imaging.

Dataset Information

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration.

Publications

Identification of lncRNAs involved in biological regulation in early age-related macular degeneration.

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