Characterization of the complete mitogenome of Gymnocypris dobula (Günther, 1868) (Cypriniformes: Cyprinidae).

Gymnocypris dobula, classified into the highly specialized Schizothoracine fish, is endemic to Tibet, China. The complete mitochondrial DNA sequence of G. dobula was 16,728 base pairs in length and comprised 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes as well as one control region as in a typical vertebrate mitochondrial DNA gene. The ML and BI trees showed that G. dobula was most closely related to Gymnocypris scleracanthus within the highly specialized group. This mitogenome provides new molecular data for further taxonomic and phylogenetic studies of Schizothoracine fish.

A relatively higher intraocular pressure set at the end of vitrectomy is associated with a more stable and rapid visual recovery for patients with vitreous haemorrhage.

PURPOSE: To compare structural and functional improvements in patients with vitreous haemorrhage (VH) with different IOPs re-established at the end of pars plana vitrectomy (PPV). METHODS: It is a prospective, randomized, comparative, interventional study. Ninety-five patients with nonclearing VH were randomized to receive PPV with normalized IOPs of 15 mmHg (Group I: 32 eyes), 25 mmHg (Group II: 32 eyes) and 35 mmHg (Group III: 31 eyes) at the end of surgery. The grade of vitreous opacity and best-corrected visual acuity (BCVA) on postoperative day 1, week 1, month 1 and month 3 were compared with a mixed model for repeated measures analysis. RESULTS: All 3 groups achieved significant improvement on postoperatively in BCVA (p < 0.01) and vitreous opacity (p < 0.01) compared with the baseline. The group difference was significant at the end of week 1 and showed a trend of higher IOP set at the end of PPV with better anatomical (p < 0.01) and visual recovery (p < 0.01). However, at postoperative month 1 and month 3, equivalent anatomical (month 1: p = 0.56; month 3: p = 0.36) and visual outcomes (month 1: p = 0.16; month 3: p = 0.88) were obtained in the 3 groups. The average effect of IOP on BCVA (group II versus group III: effect size (ES): 0.41, p < 0.01; group I versus group III: ES: 0.66, p < 0.01) and vitreous opacity (group II versus group III: ES: 0.70, p < 0.01; group I versus group III: ES:1.09, p < 0.01) over the course of the study period was statistically significant. The only postoperative complication was recurrent VH in two patients allocating in group I and II, respectively. CONCLUSIONS: A relatively higher IOP set at the end of vitrectomy resulted in a more stable and rapid recovery with fewer complications in patients with non-complex VH.

miR-590-3p Inhibits Pyroptosis in Diabetic Retinopathy by Targeting NLRP1 and Inactivating the NOX4 Signaling Pathway.

Purpose: To elucidate the mechanism whereby miR-590-3p regulates pyroptosis in diabetic retinopathy (DR). Methods: Human retinal microvascular endothelial cells (HRMECs) incubated with high glucose (HG) were used to establish cell models, and the expression levels of miR-590-3p, caspase-1, IL-1ß, NLRP1, NOX4, TXNIP, NLRP3, and ROS were determined. Additionally, miR-590-3p was altered using a mimic or an inhibitor, and siRNAs targeting NLRP1 and NOX4 were applied to explore the regulatory mechanism of miR-590-3p in DR. The relationships between miR-590-3p and NLRP1/NOX4 also were investigated using a luciferase reporter assay. Furthermore, vitreous tissue samples were collected to confirm pyroptosis in clinical DR. Results: Downregulated miR-590-3p and upregulated NLRP1/NOX4 levels were observed in a cell culture model of DR. Inhibiting miR-590-3p upregulated NLRP1, the NOX4/ROS/TXNIP/NLRP3 pathway, and caspase-1. NLRP1 and NOX4 were confirmed as direct target genes of miR-590-3p. The overexpression of miR-590-3p or knockdown of NLRP1 and NOX4 increased cell activity and suppressed pyroptosis. Intriguingly, the upregulation of IL-1ß induced the downregulation of miR-590-3p by lowering the DNA promoter activity of pri-miR-590. Conclusions: HG induced pyroptosis in a cell culture model of DR, and the downregulation of miR-590-3p promoted pyroptotic death by targeting NLRP1 and activating the NOX4/ROS/TXNIP/NLRP3 pathway via an IL-1ß-mediated positive feedback loop.

Nuclear Factor (Erythroid-Derived 2)-Like 2 (Nrf2) Contributes to the Neuroprotective Effects of Histone Deacetylase Inhibitors In Retinal Ischemia-Reperfusion Injury.

Histone deacetylase inhibitors (HDACis) have displayed neuroprotective effects in animal models of retinal ischemia/reperfusion (I/R) injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor responds to oxidative damage. We investigated the role of Nrf2 in retinal I/R injury, and further explored the mechanisms underlying Nrf2-mediated neuroprotection exerted by HDACi. High intraocular pressure was used to establish retinal I/R model in wild type (WT) and Nrf2 knockout (KO) mice. Nrf2 KO mice displayed more severe retinal damage after I/R. Trichostatin A (TSA) was administered to both WT and Nrf2 KO mice with retinal I/R damage. TSA significantly diminished the retinal ganglion cell degeneration in WT mice but offered no notable protection in Nrf2 KO mice. TSA markedly promoted Nrf2 nuclear translocation and its acetylation. In addition, TSA upregulated Nrf2 downstream proteins, such as Ho-1 and Nqo1, in retinal tissues. In the retinal neuronal cell line 661W, TSA reduced the expression of proinflammatory cytokines, Il-1ß, Il-6, Tnf-α and Mmp-9, and it upregulated Bdnf under oxidative stress. However, this trend was not continued after silencing Nrf2. Chromatin immunoprecipitation assay demonstrated that Nrf2 at the Ho-1 promoter significantly increased transcriptional activity after oxidative stress induction. Nrf2, which is dispensable in HDACi-mediated neuroprotection, plays a major neuroprotective role in retinal I/R injury.