Effects of cisplatin-5-fluorouracil combination therapy on oxidative stress, DNA damage, mitochondrial apoptosis, and death receptor signalling in retinal pigment epithelium cells.

AIM: Combination therapies of cisplatin with 5-FU (PF) are an effective solution and have been widely used for the treatment of various categories of cancer including anal, gastrointestinal, and oral cancer, as well as head and neck tumors. The effects of combined PF treatment on vital intracellular signalling pathways in nontargeted cells remain unclear. The aim of this study is to explain the possible mechanisms by which combined PF treatment results in retinal toxicity and to investigate the effects of PF on important vital signalling pathways in ARPE 19 retinal pigmented epithelial cells. MATERIALS AND METHODS: We analysed the cellular and molecular effects of PF on cell viability, oxidative stress, gene repair response, and induction of apoptosis in ARPE 19 cells using molecular probe fluorescent staining, cell cytometer, RAPD, qRT-PCR, and western blot assays. RESULTS: We determined that PF causes excessive generation of reactive oxygen species (ROS) and prevents ROS scavenging by suppressing antioxidant systems. We found induction of DNA damage, particularly mismatch and double strand break repair, in ARPE 19 cells treated with PF. In this study, PF also induced both the intrinsic apoptosis pathway and death receptor signalling in ARPE 19 cells. CONCLUSIONS: Our data proved that PF causes cytotoxicity and genotoxicity, at both the cellular and molecular levels, in ARPE 19 cells following particularly prolonged treatment (48 h). Additionally, our results suggest key molecular signals for prevention strategies that can be developed to reduce the severe side effects of PF chemotherapy.

Comparison of long-term results of trabeculectomy to treat pseudoexfoliative glaucoma and primary open angle glaucoma.

AIM: To compare the long term outcome of trabeculectomy in patients with pseudoexfoliative glaucoma (PEG) and primary open angle glaucoma (POAG) in terms of surgical success. METHODS: The success of the trabeculectomy was evaluated by three criteria. Criterion A: intraocular pressure (IOP) ≤21 mm Hg and decrease in IOP ≥20%; Criterion B: IOP ≤18 mm Hg and decrease in IOP ≥30%; Criterion C: IOP ≤15 mm Hg and decrease in IOP ≥50%. Patients that met these criteria without medical treatment were considered to be completely successful, while those that met these criteria with medical treatment were considered partially successful. Significance levels of differences between the POAG and PEG groups in the Kaplan-Meier survival curves were calculated with the log-rank test. RESULTS: Sixty-four eyes from 64 patients with PEG and 51 eyes from 51 patients with POAG were evaluated. No significant differences were detected between the PEG and POAG groups according to full or partial success relative to each of the three criteria (A: P=0.73, 0.32; B: P=0.73, 0.31; C:P=0.90, 0.27). CONCLUSION: There is no difference in the long-term success of trabeculectomy between PEG and POAG patients whose clinical characteristics are otherwise the same.

Thickness changes in foveal, macular, and ganglion cell complex regions associated with Behçet uveitis during remission.

PURPOSE: To investigate foveal, macular, and ganglion cell complex (GCC) thickness in patients with Behçet uveitis during remission. METHODS: We included patients with panuveitis attacks caused by Behçet disease. Patients were taking immunosuppressive therapy and had no active ocular inflammation. After complete ophthalmologic examination, optical coherence tomography (OCT) was performed with a macula multi-cross protocol. The OCT images were evaluated for structural changes. Patients with no structural changes were imaged with the macula map protocol to obtain parafoveal and perifoveal macular and GCC thicknesses. Patients were compared to an age-matched control group with the Mann-Whitney U test. In correlation analyses, we examined relationships among visual acuity (logMAR), disease duration, and the number of attacks. RESULTS: The study included 27 eyes of 21 patients (mean age 38.14 ± 9.18 years; mean disease duration 65.4 ± 74.6 months; mean number of attacks 2.5 ± 1.9). The OCT showed foveal thicknesses of 260.29 ± 34.17 µm in patients and 280.58 ± 19.54 µm in controls (p = 0.010). Foveal thickness was not related to visual acuity (p = 0.485), but was negatively correlated to disease duration (p = 0.016) and number of attacks (p = 0.001). Patients and controls showed similar macular thickness in parafoveal quadrants (p = 0.294, p = 0.096, p = 0.88, p = 0.111) and perifoveal quadrants (p = 0.241, p = 0.517, p = 0.53288, p = 0.241). Patient parafoveal GCCs were significantly thinner than in controls in the inferior temporal quadrant (p = 0.041), but not in other quadrants (p = 0.867, p = 0.832, p = 0.390). Patient perifoveal GCCs were significantly thicker than in controls in the superior and inferior temporal quadrants (p = 0.008, p = 0.008) and somewhat thicker (but not significantly) in the superior and inferior nasal quadrants (p = 0.052, p = 0.138). CONCLUSIONS: Patients with Behçet uveitis in remission showed insignificant decreases in foveal and macular thickness and significant increases in perifoveal GCC thickness compared to controls. The increased perifoveal GCC thickness may result from macular ischemia persisting in remission.