Quercetin Impairs the Growth of Uveal Melanoma Cells by Interfering with Glucose Uptake and Metabolism.

Monosomy 3 in uveal melanoma (UM) increases the risk of lethal metastases, mainly in the liver, which serves as the major site for the storage of excessive glucose and the metabolization of the dietary flavonoid quercetin. Although primary UMs with monosomy 3 exhibit a higher potential for basal glucose uptake, it remains unknown as to whether glycolytic capacity is altered in such tumors. Herein, we initially analyzed the expression of n = 151 genes involved in glycolysis and its interconnected branch, the "pentose phosphate pathway (PPP)", in the UM cohort of The Cancer Genome Atlas Study and validated the differentially expressed genes in two independent cohorts. We also evaluated the effects of quercetin on the growth, survival, and glucose metabolism of the UM cell line 92.1. The rate-limiting glycolytic enzyme PFKP was overexpressed whereas the ZBTB20 gene (locus: 3q13.31) was downregulated in the patients with metastases in all cohorts. Quercetin was able to impair proliferation, viability, glucose uptake, glycolysis, ATP synthesis, and PPP rate-limiting enzyme activity while increasing oxidative stress. UMs with monosomy 3 display a stronger potential to utilize glucose for the generation of energy and biomass. Quercetin can prevent the growth of UM cells by interfering with glucose metabolism.

Long-Term Effects of Botulinum Toxin A for Horizontal Concomitant Strabismus in Chinese Children.

INTRODUCTION: For childhood strabismus, early surgical intervention improves both motor and sensory outcomes. Botulinum toxin type A (BTX-A) injection is an alternative to incisional surgery that is fast, less invasive, and preserves a more normal biomechanical construct. This study was undertaken to assess the safety and effectiveness of BTX-A for horizontal concomitant strabismus in children in our institution. PATIENTS AND METHODS: Records of all children less than age 18 years with follow-up at least 12 months who were treated with BTX-A for horizontal concomitant strabismus at Beijing Children's Hospital between December 2014 and February 2021 were reviewed retrospectively. Bilateral injections of BTX-A (Henli, 1.25 IU to 5 IU/0.1 ml) were made into the medial or lateral rectus muscles according to the angle of deviation. Reinjection was permitted if the initial alignment was not satisfactory within 1 to 6 months post-injection. Motor success was defined as a final misalignment ≤10 PD. Sensory success was defined as the presence of any evidence of sensory fusion, distance stereopsis, or near stereopsis at the last visit. RESULTS: Seventy-one patients were included. Fifty-two had esotropia, and 19 had exotropia. There was a significant decrease in the angle of deviation in all treated patients. The overall motor success rate was 60.6%. The motor success rate was highest in children with esotropia <50 PD (81.5%). Motor success was better for children with partially accommodative esotropia and acquired non-accommodative esotropia (80%, 83.3%, respectively) than for children with infantile esotropia (47.4%). Compared with the esotropia group, the fusion was significantly higher in the exotropia group (p = .007), and the proportion of patients with stereoacuity of better than 100 sec arc was higher also in the exotropia group (71.4%, p = .007), evidence of sensory outcomes were significantly better in the exotropia group. Complications were few. Twenty patients (28.2%) developed transient ptosis after injections; transient vertical deviations were seen in 3 patients (4.2%); and subconjunctival hemorrhage was seen in 5 patients (7%). CONCLUSIONS: BTX-A appears to be an effective treatment for the management of horizontal strabismus with motor outcomes best in children with acquired smaller-angle esodeviations. Children with exodeviations had better sensory outcomes in this cohort. A randomized controlled study comparing incisional surgery to BTX-A will be important for guiding future treatment decisions.

Structural-visual functional relationships detected by optical coherence tomography in varying age-cohorts' patients with optic neuritis.

AIM: To assess the relationships of final best-corrected visual acuity (BCVA) and the optic nerve structural loss in varying age-cohorts of optic neuritis (ON) patients. METHODS: This is a retrospective, cross-sectional study. Totally 130 ON subjects (200 eyes) without ON onset within 6mo were included, who underwent BCVA assessment, peripapillary retinal nerve fibre layer (pRNFL) and macular segmented layers evaluation by optical coherence tomography (OCT). RESULTS: For the 0-18y cohort, the final BCVA (logMAR) was significantly better and less frequent recurrences than adult cohorts (P=0.000). The final BCVA (logMAR) in all age-cohorts of the ON patients had negative and linear correlations to the pRNFL thicknesses and macular retinal ganglion cell layer (mRGCL) volumes, when the pRNFL thicknesses were reduced to the thresholds of 57.2-67.5 µm or 0.691-0.737 mm3 in mRGCL volumes, respectively, with the strongest interdependence in the 19-40y cohort. The ON patients from varying age cohorts would be threatened by blindness when their pRNFL thicknesses dropped 36.7-48.3 µm or the mRGCL volumes dropped to 0.495-0.613 mm3. CONCLUSION: The paediatric ON has best prognosis and young adult ON exhibits perfectly linear correlations of final vision and structural loss. The pRNFL and the mRGCL could be potential structural markers to predict the vision prognosis for varying-age ON patients.

Lower Levels of Adiponectin and Its Receptor Adipor1 in the Uveal Melanomas With Monosomy-3.

Purpose: Adiponectin is an insulin-sensitizing and anticarcinogenic hormone that is encoded by a gene on chromosome 3. Here, we analyzed the expression of adiponectin and its receptor Adipor1 in primary uveal melanoma (UM) with regard to the monosomy-3 status and clinical factors, as well as the physiological response of UM cells to adiponectin. Methods: Immunohistochemistry was performed on the primary UM of 34 patients. Circulating melanoma cells (CMC) were isolated by immunomagnetic enrichment. Monosomy-3 was evaluated by Immuno-FISH. Gene expression was analyzed using the RNAseq data of The Cancer Genome Atlas study. Cultures of choroidal melanocytes and UM were established from the samples of two patients. The proliferative potential of the UM cell lines Mel-270 and OMM-2.5 was determined by immunocytochemistry, immunoblotting, cell cycle analysis, nucleolar staining, and adenosine triphosphate (ATP) levels. Results: UM with monosomy-3 exhibited a lower immunoreactivity for adiponectin and Adipor1, which was associated with monosomy-3-positive CMC and the development of extraocular growth or metastases. Both proteins were more abundant in the irradiated tumors and present in the cultured cells. Gene expression profile indicated the impairment of adiponectin-mediated signaling in the monosomy-3 tumors. Adiponectin induced a significant decline in the ATP levels, Ki-67 expression, cells in the G2/M phase, and nucleolar integrity in UM cultures. Conclusions: Adiponectin deficiency appears to enhance the metastatic potential of the UM cells with monosomy-3 and the termination of tumor dormancy. Counteracting insulin resistance and improving the serum adiponectin levels might therefore be a valuable approach to prevent or delay the UM metastases.