Abstract
Purpose :
Optic nerve head (ONH) infract can result in progressive retinal ganglion cell (RGC) death. However, molecular mechanisms of RGC death and protection after ONH ischemia are complex and remain unclear.
Methods :
To investigate the complex mechanisms involved in progressive RGC death, the transcriptome profiles following ONH infract or neuroprotection treatment were examined by microarray technology. The experiment and treatment groups were performed a laser-induced capillary vascular thrombosis to trigger ONH ischemia, and the control group undertook a sham procedure. Rats in treatment group were received subcutaneous injection with G-CSF immediately after ONH infarct. The retinal mRNA samples on day 3- and 7-post rAION in each group were analyzed by microarray and bioinformatics analyses.
Results :
G-CSF treatment influenced 3101 genes and 3332 genes on day 3- and 7-post rAION, respectively. ONH infract leaded changes in gene expression on day3-post rAION (702 genes) and day7-post rAION (179 genes). After cluster analysis, many TATA box binding protein (TBP)-associated factors were significantly reduced after ONH infarct but were significantly increased after G-CSF treatment. The network analysis revealed that TAF9 can bind P53 to induce TP53 regulated inhibitor of apoptosis 1 (TRIAP1) expression. To evaluate the TAF9 function in RGC apoptosis, the G-CSF plus TAF9 siRNA-treated rats were evaluated by using retrograde labeling with FluoroGold assay, TUNEL assay, and Western blottling in the rAION model. The RGCs density in the G-CSF plus TAF9 siRNA-treated group showed 1.95-fold (central retina) and 1.75-fold (mid-peripheral retina) lower than the G-CSF-treated group (p<0.05). The number of apoptotic RGC in the G-CSF plus TAF9 siRNA-treated group is 3-fold higher than the G-CSF-treated group (p<0.05). Treatment with TAF9 siRNA significantly reduced G-CSF-induced P53 expression and TRIAP1 expression by 2.2-fold and 4.3-fold in the rAION model.
Conclusions :
In conclusion, we believed that regulation of TAF9-P53-TRIAP1 is a crucial pathway to determine cell death fate of RGCs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.