Corneal hysteresis and Beta-zone parapapillary atrophy.

PURPOSE: To evaluate the relationship between ß-zone parapapillary atrophy (ßPPA) and corneal hysteresis (CH) in patients with glaucoma. DESIGN: Prospective, cross-sectional study. METHODS: Glaucoma patients aged 18 to 90 years with disc photographs within 12 months of the study visit were consecutively enrolled. Exclusion criteria included ocular surgery other than clear corneal phacoemulsification, myopia >6 diopters, contact lens use, and corneal abnormality. CH was measured using the Ocular Response Analyzer (ORA). Disc photographs were evaluated in a masked fashion for ßPPA. RESULTS: We enrolled 99 patients (mean age 67.6 years; 45 men, 54 women). Univariate analysis showed no significant difference in CH between eyes with and without ßPPA (8.72 ± 0.23 vs 8.15 ± 0.27 mm Hg, P = .11). There were no differences in corneal resistance factor (CRF) (P = .47), central corneal thickness (CCT) (P = .11), ORA wave score (P = .23), age (P = .23), sex (P = .40), IOP (P = .86), or visual field mean deviation (VFMD) (P = .45). Eyes with ßPPA were more myopic (-1.49 ± 0.27 vs -0.22 ± 0.31 diopters, P = .003). Multivariate analysis showed no significant difference in CH between eyes with and without ßPPA (P = .38). Eyes with asymmetric ßPPA also showed no significant difference in CH (8.97 ± 0.22 vs 9.10 ± 0.22 mm Hg, P = .69). CONCLUSIONS: We found no significant differences in CH between eyes with and without ßPPA or between fellow eyes with asymmetric ßPPA.

Spontaneous reattachment of Descemet stripping automated endothelial keratoplasty lenticles: a case series of 12 patients.

PURPOSE: To review 12 cases of postoperative detachment and spontaneous reattachment of Descemet stripping automated endothelial keratoplasty (DSAEK) lenticles. DESIGN: Retrospective, observational case series. METHODS: This was a review of patients undergoing DSAEK at 7 institutions. Patients who had a significant detachment of their DSAEK lenticle during the postoperative period were identified and divided into 2 groups. Significant detachment was defined as either complete central interface fluid with bare peripheral attachment (group 1) or a free-floating lenticle in the anterior chamber (group 2). Patients who subsequently had a spontaneous reattachment of the lenticle were identified, with data regarding surgical technique and intraoperative and postoperative complications collected for analysis. RESULTS: Our cohort consisted of 12 eyes of 12 patients who met the definition of significant postoperative detachment with subsequent spontaneous reattachment. Four patients had complete central detachment with peripheral attachment (group 1), whereas 8 patients had a free-floating lenticle (group 2). Ten of the 12 patients had a successful outcome as defined as an attached and clear DSAEK lenticle. In our study, reattachment was seen as early as 5 days and as late as 7 months after surgery, with reattachment in 9 of 12 patients by day 25. CONCLUSIONS: Spontaneous reattachment of detached DSAEK lenticles may occur during the postoperative period. The decision of when to bring the patient back for a rebubble ultimately must be made on a case-by-case basis.

The organellular chloride channel protein CLIC4/mtCLIC translocates to the nucleus in response to cellular stress and accelerates apoptosis.

CLIC4/mtCLIC, a chloride intracellular channel protein, localizes to the mitochondria and cytoplasm of keratinocytes and participates in the apoptotic response to stress. We now show that multiple stress inducers cause the translocation of cytoplasmic CLIC4 to the nucleus. Immunogold electron microscopy and confocal analyses indicate that nuclear CLIC4 is detected prior to the apoptotic phenotype. CLIC4 associates with the Ran, NTF2, and Importin-alpha nuclear import complexes in immunoprecipitates of lysates from cells treated with apoptotic/stress-inducing agents. Deletion or mutation of the nuclear localization signal in the C terminus of CLIC4 eliminates nuclear translocation, whereas N terminus deletion enhances nuclear localization. Targeting CLIC4 to the nucleus via adenoviral transduction accelerates apoptosis when compared with cytoplasmic CLIC4, and only nuclear-targeted CLIC4 causes apoptosis in Apaf null mouse fibroblasts or in Bcl-2-overexpressing keratinocytes. These results indicate that CLIC4 nuclear translocation is an integral part of the cellular response to stress and may contribute to the initiation of nuclear alterations that are associated with apoptosis.

Growth arrest in G1 protects against oxygen-induced DNA damage and cell death.

Although oxygen is required for normal aerobic respiration, hyperoxia (95% O(2)/5% CO(2)) damages DNA, inhibits proliferation in G1, S and G2 phases of the cell cycle, and induces necrosis. The current study examines whether growth arrest in G1 protects pulmonary epithelial cells from oxidative DNA damage and cell death. Mv1Lu pulmonary adenocarcinoma cells were chosen for studies because hyperoxia inhibits their proliferation in S and G2 phase, while they can be induced to arrest in G1 by altering culture conditions. Hyperoxia inhibited proliferation, increased intracellular redox, and rapidly reduced clonogenic survival. In contrast, Mv1Lu cells treated with transforming growth factor (TGF)-beta1, deprived of serum or grown to confluency, arrested and remained predominantly in G1 even during exposure. Growth arrest in G1 significantly enhanced clonogenic survival by 10-50-fold. Enhanced survival was not due to reduction in the intracellular redox-state of the cells, but instead was associated with reduced DNA strand breaks and p53 expression. Our findings suggest that the protective effects of G1 is mediated not simply by a reduction in intracellular ROS, but rather through an enhanced ability to limit or rapidly recognize and repair damaged DNA.

mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA damage and participates in the apoptotic response to p53.

mtCLIC/CLIC4 (referred to here as mtCLIC) is a p53- and tumor necrosis factor alpha-regulated cytoplasmic and mitochondrial protein that belongs to the CLIC family of intracellular chloride channels. mtCLIC associates with the inner mitochondrial membrane. Dual regulation of mtCLIC by two stress response pathways suggested that this chloride channel protein might contribute to the cellular response to cytotoxic stimuli. DNA damage or overexpression of p53 upregulates mtCLIC and induces apoptosis. Overexpression of mtCLIC by transient transfection reduces mitochondrial membrane potential, releases cytochrome c into the cytoplasm, activates caspases, and induces apoptosis. mtCLIC is additive with Bax in inducing apoptosis without a physical association of the two proteins. Antisense mtCLIC prevents the increase in mtCLIC levels and reduces apoptosis induced by p53 but not apoptosis induced by Bax, suggesting that the two proapoptotic proteins function through independent pathways. Our studies indicate that mtCLIC, like Bax, Noxa, p53AIP1, and PUMA, participates in a stress-induced death pathway converging on mitochondria and should be considered a target for cancer therapy through genetic or pharmacologic approaches.