DNA topoisomerase inhibitors are effective chemotherapeutic agents on several solid tumor cells. They induce a specific signaling cascade that executes an active cell death process (apoptosis), including caspase activation, and the blockage of the signaling is associated with drug-resistance of tumor cells. However, little is known about the initial signal transduction induced by the agents. In the present study, we screened genes that are initially upregulated in caspase-independent manner. We found that the activating transcription factor 3 (ATF3) protein, a repressor of cyclic-AMP responsive element (CRE)-dependent transcription, was strongly induced among CRE-BP/ATF members and subsequently accumulated in nuclei following camptothecin or etoposide treatment. During induction of apoptosis, the accumulation and the nuclear translocation of ATF3 coincided with the activation of caspase protease and were not inhibited by the broad caspase inhibitor Z-VAD-fmk, indicating that ATF3 induction is not a downstream event of caspase activation. When stably or transiently overexpressed, ATF3 markedly accelerated the drug-induced apoptosis and enhanced caspase protease activation. ATF3 strongly downregulated CRE-dependent transcription, while ATF3 did not affect the expression levels of Bcl-2, Bcl-x, or Bax. Our present results indicate that ATF3 plays a critical role in accelerating caspase protease activation and apoptosis. Since CRE-dependent transcription functions as cell survival signaling, ATF3 could control the upstream signaling of apoptosis by repressing CRE-dependent gene expression of cell survival factors.

The GCC is the most useful parameter to evaluate structure and function within the central 10° in glaucoma. Adjusting for RGC displacement is essential to evaluate the relationship between structure of the GCL-related layer and function at the central macula.

Peripapillary RNFL VD and thickness have different characteristic sectoral structure-function relationships in glaucoma.

Purpose: To investigate postoperative changes and prognostic factors of visual impairment after vitrectomy for unilateral epiretinal membrane. Methods: A prospective observational study on 45 eyes from 45 patients with unilateral idiopathic epiretinal membrane who underwent vitrectomy. Visual parameters (best-corrected visual acuity, metamorphopsia using M-CHARTS, and aniseikonia using the New Aniseikonia Test) and spectral domain optical coherence tomography parameters (macular retinal layer thickness and microstructure of the outer retina) were measured preoperatively and 6 and 12 months postoperatively. Statistical analyses included linear mixed-effects models for the longitudinal changes and prognostic factors of visual parameters. Results: Best-corrected visual acuity and horizontal metamorphopsia improved significantly from 6 months after surgery (P < 0.001), whereas aniseikonia decreased significantly only at 12 months (P = 0.015). Vertical metamorphopsia remained unchanged. Preoperative inner nuclear layer thickness was significantly correlated with preoperative metamorphopsia. Besides baseline values, best-corrected visual acuity had no significant prognostic factors, but preoperative ellipsoid zone disruption had a negative direction of association with postoperative metamorphopsia (coefficients: −0.37 and −0.62, P = 0.015 and 0.006 for horizontal and vertical metamorphopsia, respectively), and preoperative horizontal metamorphopsia had a positive direction of association with postoperative aniseikonia (coefficient: 1.77, P = 0.002). Conclusion: After vitrectomy, postoperative changes and prognostic factors for unilateral epiretinal membrane differed for best-corrected visual acuity, metamorphopsia, and aniseikonia.

PURPOSE.To investigate the effect of trabeculectomy on the waveform changes of laser speckle flowgraphy (LSFG) in the optic nerve head (ONH) in patients with glaucoma.METHODS. Forty-eight eyes of 48 patients with open angle glaucoma were included in this prospective study. LSFG was performed before and 1, 3, and 6 months after trabeculectomy. Longitudinal changes in average mean blur rate (MBR), blow out score (BOS), resistivity index (RI), falling rate, skew, acceleration time index, and blow out time in the tissue area of the ONH were analyzed by using mixed-effects models.RESULTS. Intraocular pressure (IOP) decreased and ocular perfusion pressure increased significantly at each postoperative time point (P < 0.001, each). BOS increased (P < 0.001, each) and RI decreased (P < 0.001, each) significantly at each postoperative time point, although average MBR and other waveform parameters did not change significantly. Multivariate analyses revealed that younger age (coefficients ¼ À0.13 and 0.0014, P ¼ 0.006 and 0.03 for BOS change and RI change, respectively), worse baseline mean deviation of visual fields (coefficients ¼ À0.18 and 0.0026, P ¼ 0.009 and 0.005), larger IOP reduction (coefficients ¼ À0.29 and 0.0037, P < 0.001, each), and larger pulse rate increase (coefficients ¼ 0.17 and À0.0024, P < 0.001, each) are significantly associated with postoperative BOS increase and RI decrease. CONCLUSIONS.Given that postoperative BOS increased and RI decreased with the average MBR remaining unchanged, IOP reduction by trabeculectomy may contribute to stable blood flow throughout the duration of the heartbeat in the tissue area of the ONH.