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EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.

ABSTRACT: Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD. Methods: We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with AMD in comparison with those from healthy controls using a publicly available dataset (GSE29801). We focused on the EFEMP1 gene, which was found to be differentially upregulated in AMD, especially in wet AMD eyes. Serological validation analysis was carried out to verify the expression of EFEMP1 in 39 wet AMD patients and 39 age- and gender-matched cataract controls, using an enzyme-linked immunosorbent assay (ELISA). We then investigated the role of EFEMP1 in angiogenesis through in vitro experiments involving EFEMP1 overexpression (OE) and knockdown in human umbilical vein endothelial cells (HUVECs). Results: An increase in EFEMP1 expression was observed in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD than in dry AMD. In addition, there was a significant increase in serum fibulin-3 (EFEMP1 encoded protein) concentration in patients with wet AMD compared with that in the controls. Tube formation and proliferation of EFEMP1-OE HUVECs increased significantly, whereas those of EFEMP1 knockdown HUVECs decreased significantly compared with those of the control. Additional extracellular fibulin-3 treatments did not increase tube formation and proliferation of wildtype and EFEMP1 knockdown HUVECs, indicating that the proangiogenic properties of EFEMP1 are of cell origin. We also found that vascular endothelial growth factor expression in HUVECs was upregulated by EFEMP1 overexpression and downregulated by EFEMP1 knockdown. Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics.

SUBMITTER: Cheng L

PROVIDER: S-EPMC7874111 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.

Cheng Lu L Chen Chong C Guo Wenke W Liu Kun K Zhao Qianqian Q Lu Ping P Yu Fudong F Xu Xun X

Frontiers in pharmacology 20210115

<b>Purpose:</b> Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD. <b>Methods:</b> We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with ...[more]

PMID: 33584252

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Project description:PurposeTo detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography.DesignObservational, cross-sectional study.ParticipantsA total of 5 normal subjects and 5 subjects with neovascular AMD were included.MethodsA total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3 × 3-mm area and comprised 200 × 200 × 8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views.Main outcome measuresThe CNV angiogram, CNV area, and CNV flow index.ResultsEn face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV.ConclusionsOptical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.

Dataset Information

EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.

Publications

EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.

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