Vitreous metabolomic signatures of pathological myopia with complications.

BACKGROUND: Pathological myopia (PM) is closely associated with blinding ocular morbidities. Identifying biomarkers can provide clues on pathogeneses. This study aimed to identify metabolic biomarkers and underlying mechanisms in the vitreous humour (VH) of PM patients with complications. METHODS: VH samples were collected from 39 PM patients with rhegmatogenous retinal detachment (RRD) (n = 23) or macular hole (MH)/myopic retinoschisis (MRS) (n = 16) and 23 controls (MH with axial length < 26 mm) who underwent surgical treatment. VH metabolomic profiles were investigated using ultra-performance liquid chromatography‒mass spectrometry. The area under the receiver operating characteristic curve (AUC) was computed to identify potential biomarkers for PM diagnosis. RESULTS: Bioinformatics analysis identified nineteen and four metabolites altered in positive and negative modes, respectively, and these metabolites were involved in tryptophan metabolism. Receiver operating characteristic analysis showed that seventeen metabolites (AUC > 0.6) in the positive mode and uric acid in the negative mode represent potential biomarkers for PM with complications (AUC = 0.894). Pairwise and pathway analyses among the RRD-PM, MH/MRS-PM and control groups showed that tryptophan metabolism and uric acid were closely correlated with PM. Altered metabolites and pathways in our study were characterized by increased oxidative stress and altered energy metabolism. These results contribute to a better understanding of myopia progression with or without related complications. CONCLUSIONS: Our study provides metabolomic signatures and related immunopathological features in the VH of PM patients, revealing new insight into the prevention and treatment of PM and related complications.

New technique for removal of perfluorocarbon liquid related sticky silicone oil and literature review.

AIM: To investigate the safety and efficacy of sticky silicone oil (SSO) removal using a 22-gauge vein detained needle and inner limiting membrane (ILM) wrap-and-peel technique. METHODS: This retrospective consecutive case series reviewed the records of patients with a history of retinal detachment who had received silicone oil and perfluorocarbon liquid (PFCL) as intraocular tamponades. Patients were included in the analysis if they exhibited SSO remnants during silicone oil removal. The aspiration of most of the SSO remnants was performed by a 22-gauge vein detained needle. The small amounts of droplets adhered to the macula and epi-macular membrane were subsequently removed by the ILM warp-and-peel technique. The anatomical and functional outcomes, and postoperative complications were recorded. In vitro experiments were performed to simulate the formation of SSO remnants in four groups. RESULTS: Of 711 patients who underwent silicone oil removal during the study period, 9 patients exhibited SSO remnants and underwent follow-up for at least 3mo. Seven eyes (78%) underwent the ILM wrap-and-peel technique to completely remove small droplets of SSO that were glued to the macula and epi-macular membrane. No obvious complications occurred. Postoperative optical coherence tomography revealed normal retinal structure in all patients. In vitro analyses showed that balanced salt solution and prolonged vibration (for 1wk) had the strongest effects on silicone oil and PFCL compound opacities. CONCLUSION: SSO remnants could be removed in an intact manner and without complications, using a vein detained needle-assisted and ILM wrap-and-peel technique. The findings suggest that PFCL and infusion fluid should be completely removed before silicone oil injection to prevent SSO formation.

Discrete functional and mechanistic roles of chromodomain Y-like 2 (CDYL2) transcript variants in breast cancer growth and metastasis.

Rationale: Chromodomain Y-like 2 (CDYL2) is a member of the CDY gene family involved in spermatogenesis, but its role in human cancer has not been reported. Analyses of publicly available databases demonstrate that CDYL2 is abundantly expressed in breast tumors. However, whether CDYL2 is involved in breast cancer progression remains unknown. Methods: Quantitative real-time PCR and immunoblotting assays were used to determine the expression levels of CDYL2 transcript variants in breast cancer cell lines and primary breast tumors. The effect of CDYL2 transcript variants on the malignant phenotypes of breast cancer cells was examined through in vitro and in vivo assays. Immunofluorescent staining, RNA-seq, ATAC-seq, and ChIP-qPCR were used to investigate the underlying mechanisms behind the aforementioned observations. Results: Here we show that CDYL2 generated four transcript variants, named CDYL2a-CDYL2d. CDYL2a and CDYL2b were the predominant variants expressed in breast cancer cell lines and breast tumors and exerted strikingly discrete functions in breast cancer growth and metastasis. CDYL2a was upregulated in the majority of the breast cancer cell lines and tumors, and promoted breast cancer cell proliferation, colony formation in vitro, and tumorigenesis in xenografts. In contrast, CDYL2b was mainly expressed in luminal- and HER2-positive types of breast cancer cell lines and tumors, and suppressed the migratory, invasive, and metastatic potential of breast cancer cells in vitro and in vivo. Mechanistically, CDYL2a partially localized to SC35-positive nuclear speckles and promoted alternative splicing of a subset of target genes, including FIP1L1, NKTR, and ADD3 by exon skipping. Elimination of full-length FIP1L1, NKTR, and ADD3 rescued the impaired cell proliferation through CDYL2a depletion. In contrast, CDYL2b localized to heterochromatin and transcriptionally repressed several metastasis-promoting genes, including HPSE, HLA-F, and SELL. Restoration of HPSE, HLA-F, or SELL expression in CDYL2b-overexpressing cells attenuated the ability of CDYL2b to suppress breast cancer cell migration and invasion. Conclusions: Collectively, these findings establish an isoform-specific function of CDYL2 in breast cancer development and progression and highlight that pharmacological inhibition of the CDYL2a, but not the CDYL2b, isoform may be an effective strategy for breast cancer therapy.

Air tamponade and without heavy liquid usage in pars plana vitrectomy for rhegmatogenous retinal detachment repair.

AIM: To report the results of rhegmatogenous retinal detachment (RRD) repair after pars plana vitrectomy (PPV) without operative use of heavy liquid, and utilizing air tamponade in selected cases. METHODS: RRD patients without severity of proliferative vitreoretinopathy C2 or more underwent PPV without operative use of heavy liquid, and utilizing air tamponade were consecutively enrolled. Alternative postoperative facedown position or lateral position was required for 3-5d. RESULTS: Totally 36 eyes of 36 patients (24 males, 66.7%) aged 53.8±10.9y underwent this modified surgery. The mean number of retinal break was 2.1±1.3. Most of the eyes (29, 80.6%) had retinal detachment involving more than one quadrant. Twenty-two (61.1%) eyes with cataract had combined phacoemulsification and intraocular lens implantation. The mean follow up time was 4.6±1.8mo. Two eyes with retinal redetachment underwent a second retinal repair surgery with silicone oil tamponade, yielding the primary reattachment rate to 94.4% (34/36). Six (16.7%) eyes had intraocular pressure higher than 25 mm Hg. The visual acuity (logMAR) improved from 0.98±0.74 preoperatively to 0.52±0.31 postoperatively (P<0.001). CONCLUSION: The success rate of this modified retinal repair surgery is comparable with traditional surgery. This technique can be considered for certain retinal detachment patients, since its apparent advantages included lower surgical complications, reduced surgery expenditure, shorter time for postoperative facedown position, and avoiding silicone oil removal surgery.

Sutureless Intrascleral Haptic-Hook Lens Implantation Using 25-Gauge Trocars.

PURPOSE: To report a new technique for sutureless intrascleral fixation of three-piece foldable intraocular lenses (IOLs) using 25-gauge trocars. METHODS: We performed this technique on patients with insufficient posterior capsule support. Seventeen eyes from 15 patients with aphakia, dislocated IOL, or subluxated crystalline lens undergoing posterior chamber sutureless implantation of an IOL were studied. The haptics of the IOL were externalized using two 25-gauge forceps. The haptics were bended back (hook-like) into the vitreous cavity through a scleral incision made by using a 25-gauge trocar. And, IOL tilt was determined by using a slit lamp and UBM, and complications were recorded. RESULTS: The IOLs were fixed with exact centration and axial stability. No wound leakage was reported even without the use of sutures. The mean best-corrected visual acuity (BCVA) was 0.82 logarithm of the minimum angle of resolution (logMAR) units preoperatively, and the mean BCVA was 0.44 logMAR units at the 6-month follow-up visit. No postoperative retinal detachment, endophthalmitis, IOL tilt or dislocation, or vitreous hemorrhage was noted. CONCLUSION: Sutureless intrascleral haptic-hook posterior chamber IOL implantation using 25-gauge trocars provides good IOL fixation with reliable wound closure without the use of sutures. This trial is registered with ChiCTR1800017436.

A modified approach to actively remove high viscosity silicone oil through 23-gauge cannula.

AIM: To report a simple approach to actively remove high viscosity silicone oil through a 23-gauge cannula via pars plana. METHODS: Forty-eight eyes of 48 patients underwent silicone oil (5700 centistokes) removal (SOR) were enrolled. A section of blood transfusion set was prepared to connect a standard 23-gauge cannula and vitrectomy machine. Silicone oil was removed with suction of 500-mm Hg vacuum through the cannula. Main outcome measures were SOR duration, number of sutured sites, intraocular pressure (IOP), best-corrected visual acuity (BCVA), and complications. RESULTS: Silicone oil was successfully removed in all cases. The mean SOR time was 5.70±0.85min. Nine eyes (18.75%) needed suture partial sclerotomies. No intraoperative complications were noted. Transient hypotony (≤8 mm Hg) was seen in 3 eyes (6.25%) on postoperative day 1, but all resolved within 1wk. Retinal reattachment was achieved in all cases and no other postoperative complications were noted during 3-month following-up. BCVA at the final visit improved or stabilized in all patients comparing to the preoperative level. CONCLUSION: Active removal of high viscosity silicone oil through a 23-gauge instrument cannula jointed with blood transfusion set is a practical and reliable technique when considering two sides of efficacy and safety.

PI3K-mediated glioprotective effect of epidermal growth factor under oxidative stress conditions.

AIM: To determine the effects of epidermal growth factor (EGF) on the proliferation and migration of Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1), and its related molecular mechanisms under normal and oxidative stress conditions. METHODS: Müller cells were cultured with different concentrations of EGF in the presence or absence of varied amounts of H2O2 and glucose oxidase (GO) which induced oxidative stress. The proliferation and migration of Müller cells were examined by 5-Bromo-2-deoxyUridine (BrdU), MTT assay, Transwell assay and scratch wound healing assays. The cell viability was determined with the MTT assay. The secretion of EGF by Müller cells was evaluated by ELISA. Western blot was performed to detect the activation of extracellular regulated protein kinases (ERK)1/2 and Akt signal pathways. RESULTS: EGF stimulated the proliferation and migration of Müller cells in a concentration-dependent manner in vitro. Under oxidative damage condition, 2h of pretreatment with 10-100 ng/mL EGF can mostly inhibit 50% lethal dose of 0.08 mmol/L H2O2-induced cell damage. The Western blot results showed that after Müller cells were exposed to varying EGF for 24h, Akt and ERK1/2 were phosphorylated in a dose-dependent manner. In the presence of the LY294002, the potent PI3K inhibitor, the p-Akt was significantly attenuated. CONCLUSION: EGF may induce the proliferation and migration of human Müller cells through the Akt and the ERK1/2 signal pathways, and induce PI3K-mediated glioprotective effect under oxidative stress.

[Effects of spirulina on serum lipids, erythrocyte membrane fluidity and vascular endothelial cells in tail-suspended rats].

OBJECTIVE: To study the changes of erythrocyte membrane fluidity, serum lipid and vascular endothelial cell caused by simulated weightlessness in rats and the beneficial effect of spirulina. METHOD: Thirty male SD rats were divided into 3 groups: free control group (group A) and two simulated weightlessness groups (groups B, C). Rats in group A and B were fed with normal forage, and the rats in group C were fed with normal forage supplemented with 5% (W/W) spirulina. Water was taken ad libitum. RESULT: Levels of serum CHO, HDL, TG, HDL-C/CHO and erythrocyte membrane fluidity decreased significantly, and number of vascular endothelial cells in plasma increased markedly in group B as compared with those in group A; The ratio of LDL-C/HDL-C, and atherosclerosis index (AI) decreased, number of vascular endothelial cells significantly lowered; level of CHO, HDL-C and value of the IDmax of plasma as well as erythrocyte membrane fluidity remarkedly increased in group C compared with those in group B. CONCLUSION: Spirulina can improve the physiological conditions of erythrocyte membrane fluidity, serum lipid and vascular endothelial cell caused by simulated weightlessness in rats.