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.

Background/aimsTo assess the role of specific visual subfields in collisions with oncoming cars during simulated driving in patients with advanced glaucoma.MethodsNormal subjects and patients with glaucoma with mean deviation <–12 dB in both eyes (Humphrey Field Analyzer 24-2 SITA-S program) used a driving simulator (DS; Honda Motor, Tokyo). Two scenarios in which oncoming cars turned right crossing the driver's path were chosen. We compared the binocular integrated visual field (IVF) in the patients who were involved in collisions and those who were not. We performed a multivariate logistic regression analysis; the dependent parameter was collision involvement, and the independent parameters were age, visual acuity and mean sensitivity of the IVF subfields.ResultsThe study included 43 normal subjects and 100 patients with advanced glaucoma. And, 5 of the 100 patients with advanced glaucoma experienced simulator sickness during the main test and were thus excluded. In total, 95 patients with advanced glaucoma and 43 normal subjects completed the main test of DS. Advanced glaucoma patients had significantly more collisions than normal patients in one or both DS scenarios (p<0.001). The patients with advanced glaucoma who were involved in collisions were older (p=0.050) and had worse visual acuity in the better eye (p<0.001) and had lower mean IVF sensitivity in the inferior hemifield, both 0°–12° and 13°–24° in comparison with who were not involved in collisions (p=0.012 and p=0.034). A logistic regression analysis revealed that collision involvement was significantly associated with decreased inferior IVF mean sensitivity from 13° to 24° (p=0.041), in addition to older age and lower visual acuity (p=0.018 and p<0.001).ConclusionsOur data suggest that the inferior hemifield was associated with the incidence of motor vehicle collisions with oncoming cars in patients with advanced glaucoma.

Background/Objectives To identify risk factors for glaucoma-related central visual field (VF) deterioration after vitrectomy with internal limiting membrane (ILM) peeling for epiretinal membrane (ERM). Subjects/Methods A prospective cohort study consisting of cases with or without glaucoma (33 eyes of 33 patients in each group) who underwent vitrectomy with ILM peeling for ERM. Humphrey 10-2 VFs and ganglion cell complex (GCC) thickness were measured at baseline and about 3, 6, and 12 months postoperatively. Longitudinal changes in VF indices and factors associated with their postoperative changes were investigated using mixed-effects models, as was sectorwise total deviation (TD) analysis using six sectors consisting of outer/inner arcuate and cecocentral sectors in each hemifield.Results VF mean deviation significantly deteriorated postoperatively only in the glaucoma group (P < 0.001). Older age, longer axial length, preoperative worse mean deviation, and thinner GCC were significant risk factors for postoperative deterioration (coefficient ± standard errors: −0.139 ± 0.067, −0.740 ± 0.241, 0.16 ± 0.07, 0.050 ± 0.020; P = 0.038, P = 0.002, P = 0.024, P = 0.012, respectively). Sectorwise analysis revealed that TD in the superior/inferior outer arcuate sectors significantly deteriorated only in the glaucoma group. Preoperative worse TD and thinner GCC were significant risk factors for deterioration in the superior outer arcuate sector (0.65 ± 0.11, 0.08 ± 0.03; P < 0.001, P = 0.042, respectively). Conclusions Central VF deterioration, especially in the outer arcuate sectors, found to be glaucoma-related changes after vitrectomy with ILM peeling for ERM. Preoperative worse VF and thinner GCC were identified as risk factors for postoperative VF deterioration.

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