Abstract
Purpose :
Abnormal neovascularization of the retina is a fundamental cause of blindness in a number of eye diseases including, retinopathy of prematurity (ROP), Diabetic retinopathy (DR) and age-related macular degeneration (AMD, wet). Mouse Müller cells (MMC) are an important source of VEGF in the retina. We have shown in previously that retinal circadian clock genes including Period1 and 2, Bmal1, VEGF and Hif1-a are critical modulators of retinal vascularizing responses and may be important participants in proliferative neovascularizing diseases. We will compare the gene expression analysis in C3f+/+ mouse retinal müller cell treated in normoxia and hypoxia to identify the genes and pathways involved in retinal neovascularization
Methods :
Purified primary C3f+/+ mouse retina Müller cells were cultured in DMEM containing 10% FBS at 37°C in a 5% CO2 incubator. The cells were serum starved for 12 hours and then were grown at 37°C for 24 hours in growth medium under both normoxic and hypoxic (O2 < 5%) conditions. Gene expression were measured by quantitative RT-PCR and RNAseq analysis. Probesets with a false-discovery rate of ≤ 0.05 were considered significantly different and were classified as cellular functions or biological pathways
Results :
There were changes in 23 genes in C3f+/+ mouse müller cell comparing normoxia and hypoxia. decreased expression of the Hif1-a signaling pathways and increased expression of VEGFa were identified
Conclusions :
The data previously suggested that mouse retinal PERIOD proteins may interact directly with HIF1a to affect protein stability; circadian clock gene network influences retinal neovascularizing responses. These data suggested that genes and pathways known to be involved in angiogenesis, as well as other biologically plausible genes and pathways, were identified. This work serves as a comprehensive resource for the study of retinal neovascularization and identification of potential rational targets for antiangiogenic therapy
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.