Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty for Iridocorneal Endothelial Syndrome With a Glaucoma Drainage Device.

PURPOSE: The purpose of this study was to evaluate the feasibility and clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) for treating iridocorneal endothelial (ICE) syndrome with a glaucoma drainage device (GDD). METHODS: In this retrospective, interventional case series, data of ICE eyes with a GDD treated with DMEK were collected at the Zhongshan Ophthalmic Center. A total of 24 patients (24 eyes) with mild-to-moderate ocular anterior segment anomalies together with good intraocular pressure (IOP) control preoperatively were included between March 10, 2014, and November 11, 2021. Cases were performed DMEK with concomitantly procedures, such as goniosynechialysis, an entire recipient's Descemet stripping, trimming of glaucoma tubes, and an inferiorly peripheral iridotomy. Graft survival, corrected distance visual acuity (CDVA), endothelial cell loss, IOP, and surgical complications were documented. RESULTS: The mean length of follow-up after surgery was 30.8 ± 7.8 months. Postoperative CDVA improved significantly. At 1 and 2 years postoperatively, 10 (50%) of 20 eyes and 7 (47%) of 15 eyes achieved a CDVA of 20/32 or better, cumulative graft success rates by Kaplan-Meier survival analysis were 89% and 67%, and endothelial cell loss were (59 ± 10)% and (71 ± 7)%, respectively. Within the follow-up period, IOP elevation and progressive peripheral anterior synechiae occurred in 7 (29%) and 5 (21%) of 24 eyes, respectively. CONCLUSIONS: With specific technical modifications, DMEK had not increased the risk of postoperative complications and provided comparable clinical outcomes in the treatment of ICE eyes with a GDD with those observed in the treatment of ICE eyes without a GDD.

Chemical-induced phase transition and global conformational reorganization of chromatin.

Chemicals or drugs can accumulate within biomolecular condensates formed through phase separation in cells. Here, we use super-resolution imaging to search for chemicals that induce phase transition within chromatin at the microscale. This microscopic screening approach reveals that adriamycin (doxorubicin) - a widely used anticancer drug that is known to interact with chromatin - specifically induces visible local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments systematically and quantitatively demonstrate that adriamycin-induced chromatin condensation is accompanied by weakened chromatin interaction within topologically associated domains, compartment A/B switching, lower chromatin accessibility, and corresponding transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1, forming fibrous aggregates in vitro. These results reveal a phase separation-driven mechanism for a chemotherapeutic drug.

Quercetin suppresses retinoblastoma cell proliferation and invasion and facilitates oxidative stress-induced apoptosis through the miR-137/FNDC5 axis.

Retinoblastoma (RB) constitutes a prevalent malignancy in clinic and usually occurs in children under the age of 5 years old. The increased frequency of malignant tumor metastases and the delayed diagnosis and treatment caused unsatisfactory therapeutic efficiency. Quercetin was formerly identified to impede tumor growth in certain malignancies. Our study attempted to investigate the effects and mechanisms of quercetin in Rb development, in order to provide an effective clinical therapeutic approach. Rb cell lines (WER1-RB1 and Y79) were incubated with different concentrations of quercetin, and then cell proliferation, invasion, apoptosis, and oxidative stress were determined. It was showed that quercetin restrained Rb cell proliferation and invasion, and induced cell apoptosis and oxidative stress in a dose dependent manner. Moreover, we found that quercetin incubation upregulated miR-137 expression in Rb cells. MiR-137 inhibition abrogated quercetin-mediated inhibition of Rb cell progression. Furthermore, dual-luciferase reporter gene assay validated that fibronectin type III domain-containing protein 5 (FNDC5) was a target for miR-137. MiR-137 overexpression restrained proliferation and invasion, and enhanced apoptosis and oxidative stress in Rb cells, whereas FNDC5 overexpression abrogated these effects. Additionally, nude mice were injected with WER1-RB1 cells to establish a xenograft tumor model, and then treated with 50 or 100 mg/kg quercetin. Quercetin treatment mitigated xenograft tumor growth in nude mice. In conclusion, quercetin restrained proliferation and invasion, and induced apoptosis and oxidative stress in Rb cells through regulating the miR-137/FNDC5 pathway. We expected that our study could provide an effective approach for Rb treatment. However, quercetin and miR-137 may have off-target effects in Rb cells, and our study still has certain limitations. Therefore, we will investigate the effects of quercetin on other signaling pathways in Rb cells and explore the application of combination therapy in follow-up experiments, in order to provide a rigorous research basis for the treatment of Rb with quercetin.