Objective To analyze the clinical outcomes of preoperative lift testing combined with levator palpebrae superioris complex (LPSC) surgery in patients with ocular myasthenia gravis (OMG) and ptosis. Design Retrospective study. Subjects, Participants, and/or Controls Twenty-six patients (41 eyes) with OMG-associated ptosis were included. No control group was involved. Methods, Intervention, or Testing Patients underwent preoperative lift testing followed by LPSC surgery. Clinical outcomes were evaluated by margin reflex distance 1 (MRD1), eyelid closure and blinking function, incidence of exposure keratitis, and pathological examination of levator muscle tissue, with postoperative follow-up of 6 months. Main Outcome Measures Changes in MRD1, surgical correction rate, eyelid function, incidence of exposure keratitis, and pathological findings. Results Preoperative lift testing predicted surgical tolerance, with 90.24% of patients passing the test. The MRD1 value significantly improved from −0.93 ± 1.55 mm preoperatively to 2.43 ± 0.42 mm at 6 months postoperatively (p < 0.001), with a complete correction rate of 90.2%. Active eyelid closure in the awake state was retained in 75% of operated eyes, complete blinking was achieved in 86.5%, and the incidence of exposure keratitis was 10%. Pathological examination revealed characteristic “sandwich-like” levator muscle fat infiltration in 56.25% of patients. Conclusion In patients with OMG and ptosis, an integrated strategy combining preoperative lift testing with LPSC surgery effectively and safely corrected severe ptosis. This approach achieved satisfactory functional and cosmetic outcomes while reducing the risk of postoperative exposure keratitis, providing a tailored surgical option for this high-risk patient population.

Corneal damage ranks among the leading causes of visual impairment globally. Given the prevalence of corneal diseases and challenges of donor cornea shortages and immune rejection, there is an urgent need to develop alternative materials for corneal repair. Although decellular corneal stroma and hydrogels modified with extracellular matrix (ECM) proteins/peptides were extensively used for corneal repair, they face the challenges such as batch to batch variation and easy proteolysis. Aiming to address these challenges, we report that the function stable and synthesis controllable β-amino acid polymer promotes keratocyte adhesion comparable to the cell adhesion gold standard RGD peptide. The optimal polymer (DM0.6CH0.4)80 modified hyaluronic acid hydrogels demonstrate remarkable efficacy in promoting keratocyte adhesion and in vivo rabbit corneal repair and obtain regenerated cornea with comparable health status to normal cornea. This synthetic polymer approach opens new avenues for the development of next-generation corneal repair materials.

Research on cholesterol and its metabolic pathways has catalyzed the development of anticancer drugs targeting cholesterol synthesis. However, the cholesterol metabolic state in melanoma remains poorly characterized. In this study, we found that total cholesterol levels and the expression of acetyl-CoA acetyltransferase 2 (ACAT2), a key cholesterogenic enzyme, were significantly elevated in melanoma cells. ACAT2-mediated de novo cholesterol synthesis promoted melanoma growth both in vitro and in vivo. Furthermore, we identified that the transcription factor SOX10, which is critical for melanocyte development, was specifically highly expressed in melanoma and directly upregulated ACAT2 expression, thereby promoting cholesterol synthesis and tumor proliferation. Mechanistically, SOX10 transcriptionally activated ACAT2 expression by interacting with TAF15. This SOX10-TAF15 complex subsequently enhanced ACAT2 protein levels, stimulated cholesterol synthesis, suppressed apoptosis, and ultimately drove melanoma proliferation. Our findings reveal that the SOX10-TAF15-ACAT2 axis is a key regulator of cholesterol synthesis and melanoma proliferation, presenting a promising therapeutic target.

Introduction: Current understanding of the immune landscape underlying allergic conjunctivitis (AC) remains rather limited. We investigated the potential association between circulating immunophenotypes and AC using Mendelian randomization (MR) methodology. Methods: Based on genome-wide association study (GWAS) summary-level statistics, a 2-sample MR was employed to analyze the bidirectional causal relationships between 731 circulating immunophenotypes and AC risk. Results: A total of 33 genetically predicted immunophenotypes were significantly associated with AC risk. A protective effect of 18 immunophenotypes against AC was found, such as CD3 on CD39(+)CD8(br) (inverse variance weighted [IVW] odds ratio [OR] = 0.936, 95% confidence interval [CI]: 0.925-0.985, p = 0.003) and CD25 on CD28(+)CD4(+) (IVW OR = 0.921, 95% CI: 0.863-0.983, p = 0.013). Conversely, 15 immunophenotypes were found to be significantly associated with AC risk, such as CD25 on IgD(-)CD38(dim) (IVW OR = 1.042, 95% CI: 1.012-1.073, p = 0.006). Reverse MR based on these 33 genetically predicted immunophenotypes suggested that AC also had a significant influence on four circulating immune cells, including CD33(-)HLA DR(-)AC (IVW OR = 1.187, 95% CI: 1.034-1.362, p = 0.015), CD3 on CD39(+)CD8(br) (IVW OR = 0.876, 95% CI: 0.779-0.985, p = 0.027), HLA DR on CD14(+)monocyte (IVW OR = 0.831, 95% CI: 0.725-0.953, p = 0.008), and CD39 on CD39(+)secreting Treg (IVW OR = 1.123, 95% CI: 1.002-1.259, p = 0.046). Conclusion: Our study highlights the intricate association between immune cells and AC, providing a valuable basis for future mechanistic and therapeutic studies from an immunological perspective.

To analyze intraorbital Hydroxyapatite(HA) implant exposure occurring beyond ten years of implantation and suggest potential contributing factors. A retrospective cohort study based in the Shanghai Ninth People’s Hospital. One hundred and one Chinese patients with HA implant exposure were identified, from which 38 patients with implants exposure after ten years of insertion were selected and analyzed for demographic and medical records, clinical manifestations, surgery type, implant size, exposure area, follow-up duration, complications, details regarding prosthesis care, and treatment methods. All of the removed implants were sent for an HE pathologic examination. The 38 cases experienced exposure 10 to 19 years after implantation and presented to the clinic with increased secretions, proliferation of granulation tissue, visible suture exposure, and difficulty in wearing the external prosthesis. Other complications included implant forward position in 3 patients, eyelid retraction in 4 patients, and all the patients presented with post-enucleation socket syndrome. Reviewing the medical history, HA implant sizes ranged from 18 to 22 mm. Fourteen patients underwent implant repair surgery, of which 2 experienced recurrence, and ultimately, 26 implants were removed. Of the 26 removed implants, histologic examination showed that 17 exhibited chronic infection, and 12 had limited fibrovascular ingrowth. The questionnaires indicated that 26 patients did not renew the external prosthesis regularly. This study identified late complications and potential risk factors for implant exposure beyond ten years of implantation, including chronic infection, non-absorbable sutures, and low and delayed vascularization.

IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the LatY136F mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12+ cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.

Objective: To evaluate the surgical outcomes of a modified technique for treating congenital cilial entropion in children, which involves reducing tension step by step in the epicanthus and lower eyelid incision. Methods: The observational group consisted of 153 pediatric patients (81 males and 72 females ) who were treated using the modified technique, whereas the control group included 124 patients (68 males and 56 females ) who were treated using the rotating suture surgery. All the participants were bilateral. Surgical outcomes were classified as good, fair, or poor, and the recurrence rate, scar condition, inferior eyelid position, and patient satisfaction were also assessed. Results: The mean follow -up period was 9.13 +/- 3.50 months (range: 3-14 months ) for the observational group and 6.93 +/- 4.51 months (range: 3-14 months ) for the control group. In the observational group, surgical success with "good" outcomes was achieved in 300 eyes (98.04% ), compared to 224 eyes (90.32% ) in the control group. No recurrence occurred in the observational group, whereas the recurrence rate in the control group was 4.43%. Postoperative scar formation was mild in the observational group. The average scar score was 1.27 +/- 0.96 in the observational group and 2.70 +/- 0.99 in the control group, with a statistically significant difference (P < 0.001 ). Neither overcorrection nor postoperative ectropion was observed in both groups. Conclusion: The modified technique effectively corrected medial entropion and trichiasis in the lower eyelid, resulting in stable postoperative outcomes, mild scar formation, quick recovery, flexible eyelid motility, and stable ocular surface. Therefore, it can be widely applied to children with congenital entropion and trichiasis. (c) 2024 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.

This study aims to determine the influence of vitrectomy combined with macular epiretinal membrane dissection and internal limiting membrane (ILM) peeling and phacoemulsification on choroidal vasculature in patients with unilateral idiopathic epiretinal membrane (IERM) and concurrent cataract using optical coherence tomography (OCT). This retrospective study included 26 eyes of 26 patients (8 males and 18 females) with unilateral IERM without vitreomacular traction (VMT) (group 1) and the patients’ fellow eyes (n = 26, group 2). Three-port 25-G pars plana vitrectomy (PPV) combined with macular epiretinal membrane dissection and ILM peeling and phacoemulsification was performed on all patients. The comprehensive ophthalmologic examinations of all patients involved OCT measurements at every visit before and after surgery, and the choroidal thickness (CT), central macular thickness (CMT) and choroidal vascularity index (CVI) were calculated. The mean age of the IERM patients was 66.58 ± 7.06 years. Postoperatively, best corrected visual acuity (BCVA) was significantly greater than baseline (P = 0.023). The CVI of the IERM eyes was significantly lower (P < 0.01) than that of the fellow eyes at baseline. The subfoveal CT in the IERM eyes was lower than that in the fellow eyes (P = 0.023), but there was, no significant difference in the average CT between the two groups at baseline (P = 0.071). In eyes with IERM, the CVI significantly increased at 1 week, 1 month (P < 0.001), and 3 months (P = 0.049) postoperatively, the subfoveal CT was markedly thickened 1 month after surgery (P = 0.001), the temporal 3 mm and nasal CT significantly increased at 1 week and 1 month postoperatively (P = 0.041, P = 0.022 for temporal 3 mm; P < 0.001, P = 0.047 for nasal 1.5 mm; P = 0.01, P = 0.001 for nasal 3 mm), and only the temporal 3 mm CT increased significantly at 3 months postoperatively (P = 0.017). The baseline CMT of the IERM eyes was significantly thicker than that of the fellow eyes (P < 0.001). CMT significantly decreased at 3 months postoperatively in IERM eyes(P = 0.033). The increase in the CVI in the IERM eyes without VMT after combined PPV with ILM peeling and phacoemulsification persists for at least 3 months.

To evaluate the surgical outcomes of pediatric congenital blepharoptosis with poor Bell’s phenomenon (BP) treated with modified levator muscle complex suspension. Forty-two pediatric congenital blepharoptosis patients with poor BP were treated with modified levator muscle complex suspension, and their major surgical outcomes such as marginal reflex distance1 (MRD1), palpebral fissure height (PFH), and postoperative lagophthalmos were retrospectively reviewed. The mean follow-up was 10.28 ± 9.89 months (range 3–32 Months). Surgical success was achieved in 54 (87.1%) of 62 eyelids at the final visit, including excellent results in 46 (74.2%) eyelids, good results in 8 (12.9%) eyelids, and poor results in 8 (12.9%) eyelids, respectively. The postoperative PFH of affected eyes (7.97 ± 1.47 mm) was significantly improved compared with that before surgery (3.58 ± 1.31 mm). The mean MRD1 was improved from − 1.48 ± 1.36 mm before surgery to 2.94 ± 1.46 mm after surgery. The postoperative MRD1 was ≥ 3 mm in 46 eyelids and < 3 mm in 16 eyelids. The mean lagophthalmos was 1.42 ± 1.20 mm 3 months after surgery. All of the patients presented complete blink postoperatively. Postoperative complications were rarely observed during follow-up. No patient had exposure keratitis, but blepharoptosis recurred in 6 patients (8 eyelids). All patients had satisfactory eyelid symmetry and contour. No complications were observed until the last visit. The modified method results complete blink, mild, and quick recovery of lagophthalmos, flexible eyelid motility, stable ocular surface, and it is simple to perform with few complications and a low recurrence rate at 12.9%, which is worth to wide application on poor Bell’s phenomenon blepharoptosis.

Purpose The aim of this study was to explore the effect of congenital ptosis on the visual function of patients and observe the improvement in visual function after the correction of ptosis at different surgical times. Methods We performed a retrospective study of 265 patients (346 eyes) with congenital ptosis at the same hospital. Each patient underwent an ophthalmic examination, including optometry and measurement of the affected palpebral fissure height and upper eyelid margin reflex distance. Preoperative clinical and morphologic data were compared with postoperative data. Results The refractive error of the patient population was significantly different from that of the general population ( P < 0.01). The rates of strabismus and amblyopia were 12.45% and 36.98%, respectively, in the ptosis patients, both of which are higher than the rates in the general population ( P < 0.01), especially for unilaterally affected patients and patients with the optical axis covered. The refractive error of patients younger than 5 years was improved postoperatively ( P < 0.05). The number of cases of amblyopia and strabismus was reduced, as was the percentage of cases of with-the-rule astigmatism ( P < 0.05). Conclusion Congenital ptosis can result in refractive error, strabismus, and amblyopia, which could seriously impair the visual function of patients. The impairment is more pronounced in unilaterally affected patients. Surgery is conducive to the recovery of visual function, especially in patients younger than 5 years. Satisfactory curative effects can be obtained before the age of 3 years; thus, unilaterally affected patients, severely affected patients, and patients with impaired visual function should undergo surgery as soon as possible.

Melanoma cells exhibit increased aerobic glycolysis, which represents a major biochemical alteration associated with malignant transformation; thus, glycolytic enzymes could be exploited to selectively target cancer cells in cancer therapy. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) switches glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate by coupling with the reduction of NAD+ to NADH. Here, we demonstrated that GAPDHS displays significantly higher expression in uveal melanoma (UM) than in normal controls. Functionally, the knockdown of GAPDHS in UM cell lines hindered glycolysis by decreasing glucose uptake, lactate production, adenosine triphosphate (ATP) generation, cell growth and proliferation; conversely, overexpression of GAPDHS promoted glycolysis, cell growth and proliferation. Furthermore, we identified that SOX10 knockdown reduced the activation of GAPDHS, leading to an attenuated malignant phenotype, and that SOX10 overexpression promoted the activation of GAPDHS, leading to an enhanced malignant phenotype. Mechanistically, SOX10 exerted its function by binding to the promoter of GAPDHS to regulate its expression. Importantly, SOX10 abrogation suppressed in vivo tumor growth and proliferation. Collectively, the results reveal that GAPDHS, which is regulated by SOX10, controls glycolysis and contributes to UM tumorigenesis, highlighting its potential as a therapeutic target.

Orbital fractures generally do not cause eyelid malposition. Studies have shown that mostly eyelid malposition is mainly due to the choice of surgical approaches of orbital fracture repair. Approaches are divided into transcutaneous and transconjunctival ones. The application of orbital fracture approaches depends on fractures’ range and the surgeons’ preferences. Eyelid malposition after orbital fracture surgery is not only an aesthetic concern but also a functional complication, which will cause eyes discomfort, such as corneal exposure and ocular irritation. Some patients may have multiple types of eyelid malposition. In this review, we summarized the surgical approaches of orbital fractures and the complications including scar, ectropion, retraction, entropion, flattening, laceration and lacrimal canaliculus avulsion and notch deformity that associated with eyelid, especially the lower eyelid. Reports revealed that the scar usually occurred in infraorbital incisions compared with subtarsal and subciliary incisions, and the transconjunctival approach had a higher incidence of entropion and flattening, and less ectropion than the transcutaneous approach. Meanwhile, pathogenesis of eyelid malposition after orbital fracture surgery are discussed. Furthermore, to prevent eyelid malposition complications, doctors should choose the appropriate orbital fracture approach according to the patient’s needs, and delicate tissue management, technical expertise, and meticulous hemostasis are necessary. Conservative treatment with taping, lubricating ointment, and steroid for eyelid malposition complications should be performed first, and then surgical intervention when the conservative

AIM: To conduct a systematic review and Meta-analysis of the published literature to evaluate the pooled prevalence rate of amblyopia in patients with congenital ptosis. METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP databases for studies reporting the prevalence of amblyopia in patients with congenital ptosis. The reference lists of relevant studies were scanned. Heterogeneity of effect sizes across studies was tested. We calculated prevalence ratios to compare prevalence estimates for different causes of amblyopia in patients with congenital ptosis, as well as for different geographical regions, year of publication and sample size in subgroup analyses. A systematic review and Meta-analysis were performed. RESULTS: We identified 29 eligible surveys with a total population of 2436. Prevalence rates of amblyopia ranged from 13.8% to 69%. We noted substantial heterogeneity in prevalence estimates for amblyopia in congenital ptosis (Cochran's χ2 significant at P<0.0001; I2=90%). The pooled prevalence using random-effects models of 29 studies was 32.8% (95%CI: 27.3%-38.4%) in the overall population. Compared to the overall pooled prevalence, amblyopia prevalence was higher in studies in which only subjects with blepharophimosis syndrome were included. CONCLUSION: We confirm that nearly one-third of congenital ptosis patients are suffering from or at risk for amblyopia. Patients with blepharophimosis syndrome are more likely to develop amblyopia. The identification and management of amblyopia should be integral to the treatment of congenital ptosis.

Purpose: Facial paralysis (FP) leads to diverse periocular complications which threats visual acuity and affects corneal nerve functionally and morphologically. This study aims to summarize the clinical ophthalmic outcomes, corneal sensation, and morphological alterations of subbasal nerve and dendritic cells (DCs) in patients with facial paralysis. Methods: We performed a cross-sectional study of 48 consecutive patients with facial paralysis at one tertiary hospital. Forty-eight healthy participants were enrolled as controls. The images of corneal nerves and epithelial DCs were detected by in vivo confocal microscopy (IVCM). Each patient received thorough ophthalmic examination, tear film function tests, corneal fluorescence staining and Cochet-Bonnet esthesiometry test. Clinical and morphologic data were compared with controls. Results: Forty patients (83.3%) showed corneal injuries from punctate epithelial defects to corneal ulcers and scars. Visual impairment and eyelid malposition were observed. Corneal sensitivity remarkably decreased (25.1 +/- 23.8 mm) in the affected eyes and was correlated to diminished subbasal nerve density (P = .019, r = 0.387). Numbers of corneal main nerve trunks and branches were significantly reduced (P < .0001) while DCs were increased (P < .0001) in patients with FP when compared with controls. Nerve fiber density showed inverse association with DC density (P = .019, r = -0.389). Conclusions: Ocular complications including corneal erosions, loss of corneal sensation, visual impairment and eyelid malposition have largely affected patients with facial paralysis. Morphological changes of diminished corneal subbasal nerve and increased DCs were detected by IVCM. Corneal epithelial defect, corneal opacity, corneal sensation, dendritic cell density are factors associated with corneal subbasal nerve density. Patients with FP are suggested to have complete ophthalmic evaluation and early instruction on ocular prevention.

Purpose: To explore the pathogenesis that TIMP-1 mediated in adult orbital xanthogranulomatous disease (AOXGD), a rare type of non-Langerhans histiocytosis that damages the appearance and quality of life of patientsMethods: We reviewed 22 patients diagnosed with AOXGD based on clinical manifestations and histological analysis, and then investigated the expression of TIMP-1 and IL-6 with q-PCR and IHC in AOXGD tissues and the possible mechanism involved in the induction of TIMP-1 by IL-6.Results: IL-6 and TIMP-1 were significantly increased in AOXGD tissues. IL-6 promoted TIMP-1 production by M1 macrophages by stimulating the phosphorylation of JAK2 and STAT3. Moreover, IL-17 and IFN-γ, the classical markers of Th1 and Th17 cells, were increased in AOXGD.Conclusion: These data implied that the IL6~JAK2/STAT3-TIMP-1 signalling pathway is activated in AOXGD and that adaptive Th1 and Th17 responses are involved in the development of AOXGD.

Goldenhar syndrome has variable presentations and can affect multiple regions of the body. Diagnoses are based on clinical manifestations. The association of Goldenhar syndrome with blepharophimosis and limb deformities has not previously been reported. Here, we describe a patient who was diagnosed with Goldenhar syndrome in association with blepharophimosis, ocular hypertelorism, hearing loss and limb deformities.

Background This study aims to evaluate the effect of a modified approach on severe congenital ptosis treatment. Methods Through anterior approach, Müller muscle was preserved, meanwhile the upper tarsus was suspended to combined fascia sheath (CFS) and levator muscle (LM) complex. The main outcome measures included marginal reflex distance1 (MRD1), palpebral fissure height (PFH), MRD1 regression, MRD1 improvement, and patient self-satisfaction. Results There were 70 patients (90 eyelids) with severe congenital ptosis received treatment of modified operation, including 20 bilateral and 50 unilateral ptosis. The average LF was 2.53 ± 1.06 mm. The preoperative MRD1 and PFH was −0.06 ± 0.76 mm and 4.25 ± 0.85 mm, respectively. The follow-up was at least 6 months with average of 12.67 ± 4.92 months. The immediate postoperative MRD1 and PFH average was 4.52 ± 0.39 mm and 9.24 ± 0.26, respectively. The last follow-up MRD1 and PFH average was 2.43 ± 0.57 mm and 7.16 ± 0.69 mm, respectively, which was improved significantly (P < 0.01). There were variety degrees of MRD1 regression especially in the first month after operation, and the last follow-up MRD1 regression was 2.09 ± 0.67 mm. The lagophthalmos was obvious immediately after operation and regularly released after 6 months. Objective curative effect assessment showed 78 (86.7%) satisfactory eyes, 4 (4.4%) improved eyes, and 8 (8.9%) noneffective eyes. Two noneffective eyes required reoperation of frontalis suspension. Self-satisfaction rate was 93.3%. Parameters analysis showed that LF had positive correlation with last follow-up MRD1 and negative correlation with MRD1 improvement (P < 0.01). Five eyes had levator shorten history, which was associated remarkably with CFS + LM curative effect (P < 0.01). Mean swelling time was 0.53 ± 0.41 months, and no complications were observed until the last visit. Conclusions This modified method gives powerful correction and vivid eyelid contour, featured with simple surgical procedures, few complications, and satisfactory effect, which is worth to wide application.

Hypoxia-inducible factor-1 (HIF-1) is a key transcriptional factor responsible for the expression of a broad range of genes that facilitate acclimatization to hypoxia. Its stability is predominantly controlled by rapid hydroxylation of two prolines on its α subunit. However, how the rapid hydroxylation of HIF-1α is regulated is not fully understood. Here, we report that transient receptor potential canonical (TRPC) 6 channels control hydroxylation and stability of HIF-1α in human glioma cells under hypoxia. TRPC6 was rapidly activated by IGF-1R-PLCγ-IP3R pathway in hypoxia. Inhibition of TRPC6 enhanced the levels of α-ketoglutarate (α-KG) and promoted hydroxylation of HIF-1α to suppress HIF-1α accumulation without affecting its transcription or translation. Dimethyloxalylglycine N-(methoxyoxoacetyl)-glycine methyl ester (DMOG), an analog of α-KG, reversed the inhibition of HIF-1α accumulation. Moreover, TRPC6 regulated GLUT1 expression depending on HIF-1α accumulation to affect glucose uptake in hypoxia. Our results suggest that TRPC6 regulates metabolism to affect HIF-1α stability and consequent glucose metabolism in human glioma cells under hypoxia.

OBJECTIVE:To investigate the essential role and mechanism of TRPC6 gene in the development of gastric cancer.METHODS:The expression of TRPC6 protein was assessed in gastric cancer tissues and normal tissues adjacent to the cancer from 30 patients with gastric cancer. The inhibiting effect of TRPC6 activity on cell growth, cell cycle of a human gastric cancer cell line AGS cells, tumor progression and development of xenografted human gastric cancer in a mouse model was tested using dominant-negative mutant TRPC6 (DNC6). The survival of mice bearing xenografted tumors in the GFP and DNC6 was compared using Kaplan-Meier analysis. All statistical tests were two-sided.RESULTS:The TRPC6 protein in the tumor tissues and para-tumor tissues was (21.60 ± 8.32)% versus (7.14 ± 2.24)%. After transfection of DNC6 virus for 24 hours, 48 hours, 72 hours and 96 hours, the growth inhibition rates of gastric cancer cells were (36.90 ± 1.13)%, (44.06 ± 2.17)%, (52.12 ± 2.76)% and (50.89 ± 1.97)%, respectively. The clone formation rates of control group and DNC6 group were (14.70 ± 3.00)% versus (43.80 ± 7.00)%. After transfection with DNC6 virus for 0, 24, 36 and 48 hours, the G(2)/M phase arrest was (20.34 ± 1.98)%, (24.31 ± 2.37)%, (27.70 ± 2.36)%, (35.10 ± 3.0)% in the DNC6 group and (18.40 ± 2.01)%, (18.0% ± 1.72)%, (17.50 ± 1.74)%, (16.80 ± 1.71)% in the control group, respectively. Inhibition of TRPC6 activity also reduced the subcutaneous tumor volume in the mouse models with xenografted human tumors (P < 0.05).CONCLUSION:In the preclinical models tested, TRPC6 channels are essential for gastric cancer development via regulation of G(2)/M phase transition.