期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 60, 期 13, 页码 4084-4096出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.19-26767
关键词
proliferative diabetic retinopathy; transcriptome profile; VEGF; ETS transcription factors; neovascularization
资金
- National Natural Science Foundation of China [81272242, 81502284]
- National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology [2013ZX09103003004]
- Fundamental Research Funds for the Central Universities
- Grant of Jilin Province Science & Technology Committee, China [20170414028GH, 20170520031JH, 201706230TC, 20150204038YY, 20150101188JC, 20150309003YY]
- Beauty of Life, Inc. [2014-11032]
PURPOSE. To investigate whole transcriptional differences between proliferative diabetic retinopathy (PDR) neovascular membranes (NVMs) and retinas, and the regulatory genes participating in retinal neovascularization in PDR. METHODS. We used high-throughput sequencing technology to capture the whole-genome gene expression levels of all participants, including 23 patients with PDR or branch retinal vein occlusion (BRVO), 3 normal retinal samples, and 2 retinal samples from type II diabetic (T2D) eyes by donation, followed by analyses of expression patterns using bioinformatics methods, then validation of the data by in situ hybridization and Western blotting. RESULTS. We showed that transcriptional profiles of the NVMs were distinct from those of the retinas. Angiogenesis growth factors VEGFC, ANGPT1, ANGPT2, and EFNB2, and their receptors FLT4, TIE1, TIE2, and EPHB4, respectively, were overexpressed. Expression of VEGFA was highly upregulated in T2D retina, but low in the NVMs, while angiogenesis transcription factors, including ETS1 and ERG, were coordinately upregulated in NVMs. CONCLUSIONS. This study described a PDR neovascularization model in which pathological retina-secreted vascular endothelial growth factor A (VEGFA) enhanced the expression of a set of angiogenesis transcription factors and growth factors, to cooperatively induce the retinal neovascularization. Based on these results, novel potential therapeutic targets and biomarkers for PDR treatment and diagnosis are suggested.
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