Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Surgical strategy and outcome in patients with bilateral proliferative diabetic retinopathy.

OBJECTIVES: To investigate the current surgery strategies for bilateral proliferative diabetic retinopathy (PDR), as well as the surgical outcomes of patients with bilateral PDR who underwent pars plana vitrectomy (PPV). MATERIALS: Patients undergoing bilateral vitrectomy for PDR from January 2019 to December 2020 at The Eye Hospital of Wenzhou Medical University were enrolled. Clinical data were collected from the electronic medical records. Factors associated with the time interval between the surgeries on two eyes and postoperative visual outcomes were analyzed. RESULTS: In total, 152 patients with bilateral PDR who underwent bilateral PPV were included in this analysis. Mean age was 53.7 ± 11.4 years. Compared with second-surgery eyes, 60.5% of first-surgery eyes had worse preoperative best-corrected visual acuity (BCVA). The overall PPV time (median, quartile range) between first and second surgeries eye was 1.40 (0.70, 3.15) months. Multivariate analysis showed that the preoperative BCVA of the second-surgery eye had a significant effect on the inter-surgery time interval (P = 0.048). First-surgery eyes had greater vision improvement than second-surgery eyes (Difference of the logarithm of the minimum angle of resolution [LogMAR] BCVA: - 1.00 [- 1.48, - 0.12] versus 0.00 [- 1.30, 0.00], respectively, P < 0.001), especially when eyes with poorer BCVA underwent PPV first (- 1.15 [- 1.87, - 0.54] versus 0.00 [- 0.70, 0.00], respectively, P < 0.001). CONCLUSIONS: Visual acuity is a significant factor that influences surgical strategies, including both surgery order and interval, for patients with bilateral PDR. The eyes operated upon first show more vision improvement due to prompt surgery.

Enhanced putamen functional connectivity underlies altered risky decision-making in age-related cognitive decline.

Risky decision-making is critical to survival and development, which has been compromised in elderly populations. However, the neural substrates of altered financial risk-taking behavior in aging are still under-investigated. Here we examined the intrinsic putamen network in modulating risk-taking behaviors of Balloon Analogue Risk Task in healthy young and older adults using resting-state fMRI. Compared with the young group, the elderly group showed significantly different task performance. Based on the task performance, older adults were further subdivided into two subgroups, showing young-like and over-conservative risk behaviors, regardless of cognitive decline. Compared with young adults, the intrinsic pattern of putamen connectivity was significantly different in over-conservative older adults, but not in young-like older adults. Notably, age-effects on risk behaviors were mediated via the putamen functional connectivity. In addition, the putamen gray matter volume showed significantly different relationships with risk behaviors and functional connectivity in over-conservative older adults. Our findings suggest that reward-based risky behaviors might be a sensitive indicator of brain aging, highlighting the critical role of the putamen network in maintaining optimal risky decision-making in age-related cognitive decline.

Aging-related changes in reward-based decision-making depend on punishment frequency: An fMRI study.

Introduction: Aging is often accompanied by significant cognitive decline and altered decision making. Previous studies have found that older adults have difficulty in processing reward/risk information, leading to suboptimal decision strategy. However, it is still under investigated about the neural substrates of risky decision-making under ambiguity in aging. Methods: Using the Iowa Gambling Task, the current study investigated inter-individual differences of risk-taking behaviors in healthy older adults with task-related functional magnetic resonance imaging. Results: It was found that participants were able to improve their decisions in advantageous decks, but failed to avoid disadvantageous decks during task performance. The task-related activations within multiple brain regions were observed significantly different across the four decks, and showed negative correlations with age in disadvantageous decks but not in advantageous decks. Consistently, age-related whole brain analyses confirmed the negative age-effect on brain activations in disadvantageous decks, especially in high punishment frequency. In addition, the relationship between age and task performance in high punishment frequency was mediated by activation in the frontal subregions such as the middle frontal cortex and superior medial frontal cortex. Discussion: Our findings shed light on the neural substrates of altered risk-taking behaviors in aging, suggesting a greater sensitivity to high punishment frequency in older adults.

Incidence of rhegmatogenous retinal detachments is increasing in Wenzhou, China.

AIM: To estimate and compare the incidence and characteristics of rhegmatogenous retinal detachments (RRDs) in the Wenzhou area in 2015 to 2019. METHODS: All newly developed RRD cases among residents of the Wenzhou area, from January 2015 to December 2019, were retrospectively retrieved from hospital records. Annual population data were extracted from the Wenzhou Statistical Yearbook. RESULTS: There were 3629 eligible cases. The average incidence of RRD was 7.79 cases per 100 000 population (95% confidence interval, 7.24-8.34), and the incidences were 7.99 and 7.56 for males and females, respectively. The annual incidence increased gradually from 7.26 cases per 100 000 in 2015 to 10.00 cases per 100 000 in 2019, with an overall increase of 37.74%. The highest rate of increase occurred in the age group from 60 to 69 years. Of 2750 eyes with axial length (AL) data, 1675 (60.91%) had an AL greater than 24 mm. CONCLUSION: A trend to increasing RRD incidence is observed in the Wenzhou area over the past 5-year period.

Corrigendum: Tonoplast proton pumps regulate nuclear spacing of female gametophytes via mediating polar auxin transport in arabidopsis.

[This corrects the article DOI: 10.3389/fpls.2022.1006735.].

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.

Hyper-inflammation of astrocytes in patients of major depressive disorder: Evidence from serum astrocyte-derived extracellular vesicles.

Astrocyte-derived extracellular vesicles (ADEs) allow the in vivo probing of the inflammatory status of astrocytes practical. Serum sample and ADEs were used to test the inflammatory hypothesis in 70 patients with major depressive disorder (MDD) and 70 matched healthy controls (HCs). In serum, tumor necrosis factor α (TNF-α) and interleukin (IL)-17A were significantly increased, where as IL-12p70 was significantly reduced in the MDD patients compared with HCs. In ADEs, all inflammatory markers (Interferon-γ, IL-12p70, IL-1ß, IL-2, IL-4, IL-6, TNF-α, and IL-17A) except IL-10 were significantly increased in the MDD patients, the Hedge's g values of elevated inflammatory markers varied from 0.48 to 1.07. However, there were no differences of all inflammatory markers whether in serum or ADEs between MDD-drug free and medicated subgroups. The association of inflammatory biomarkers between ADEs and serum did not reach statistically significance after multi-comparison correction neither in the HCs nor MDD patients. The spearman coefficients between inflammatory factors and clinical characteristics in the MDD patients, such as onset age, disease course, current episode duration, and severity of depression, were nonsignificant after multi-comparison correction. In the receiver operating characteristic curves analysis, the corrected partial area under the curve (pAUC) of each inflammatory markers in ADEs ranged from 0.522 to 0.696, and the combination of these inflammatory factors achieved a high pAUC (>0.9). Our findings support the inflammatory glial hypothesis of depression, and suggests that in human ADEs could be a useful tool to probe the in vivo astrocyte status.

Age of onset for major depressive disorder and its association with symptomatology.

BACKGROUND: The age of onset (AOO) is a key factor for heterogeneity in major depressive disorder (MDD). Looking at the effect of AOO on symptomatology may improve clinical outcomes. This study aims to examine whether and how AOO affects symptomatology using a machine learning approach and latent profile analysis (LPA). METHODS: The study enrolled 915 participants diagnosed with MDD from eight hospitals across China. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale. The relationship between symptom profiles and AOO was explored using Random Forest. The effect of AOO on symptom clusters and subtypes was investigated using multiple linear regression and LPA. A continuous AOO indicator was used to conduct the analyses. RESULTS: Based on the Random Forest, symptom profiles were closely associated with AOO. The regression model showed that the severity of neurovegetative symptoms was positively associated with AOO (ß = 0.18, p < 0.001), and the severity of cognitive-behavioral symptoms was negatively associated with AOO (ß = -0.12, p < 0.001). LPA demonstrated that the subgroups characterized by suicide and guilt had earlier onset of depression. The subgroup with the lowest global severity of depression had the latest onset. LIMITATIONS: AOO was recalled retrospectively. The relative scarcity of participants with childhood and adolescence onset depression. CONCLUSIONS: AOO has an important impact on symptomatology. The findings may enhance clinical evaluations for MDD and assist clinicians in promoting earlier detection and individualized care in vulnerable individuals.

TNF-α, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms.

Background: The association between inflammation and major depressive disorder (MDD) remains poorly understood, given the heterogeneity of patients with MDD. Aims: We investigated inflammatory markers, such as interleukin (IL)-6, high-sensitivity C reactive protein (hsCRP) and tumour necrosis factor-α (TNF-α) in melancholic, atypical and anxious depression and explored whether baseline inflammatory protein levels could indicate prognosis. Methods: The sample consisted of participants (aged 18-55 years) from a previously reported multicentre randomised controlled trial with a parallel-group design registered with ClinicalTrials.gov, including melancholic (n=44), atypical (n=37) and anxious (n=44) patients with depression and healthy controls (HCs) (n=33). Subtypes of MDD were classified according to the 30-item Inventory of Depressive Symptomatology, Self-Rated Version and the 17-item Hamilton Depression Rating Scale. Blood levels of TNF-α, IL-6 and hsCRP were assessed using antibody array analysis. Results: Patients with MDD, classified according to melancholic, atypical and anxious depression subtypes, and HCs did not differ significantly in baseline TNF-α, IL-6 and hsCRP levels after adjustment. In patients with anxious depression, hsCRP levels increased significantly if they experienced no pain (adjusted (adj.) p=0.010) or mild to moderate pain (adj. p=0.038) compared with those with severe pain. However, the patients with anxious depression and severe pain showed a lower trend in hsCRP levels than patients with atypical depression who experienced severe pain (p=0.022; adj. p=0.155). Baseline TNF-α (adj. p=0.038) and IL-6 (adj. p=0.006) levels in patients in remission were significantly lower than those in patients with no remission among the participants with the atypical depression subtype at the eighth-week follow-up. Conclusions: This study provides evidence of differences in inflammatory proteins in patients with varied symptoms among melancholic, atypical and anxious depression subtypes. Further studies on the immunoinflammatory mechanism underlying different subtypes of depression are expected for improved individualised therapy. Trial registration number: NCT03219008.

Tonoplast proton pumps regulate nuclear spacing of female gametophytes via mediating polar auxin transport in Arabidopsis.

The vacuole is an important organelle with multiple functions in plants, and the tonoplast that wraps the vacuole also plays essential roles in intracellular trafficking and ion homeostasis. Previous studies found that tonoplast proton pumps regulate embryo development and morphogenesis through their effects on vacuole biogenesis and distribution, as well as polar auxin transport and concomitant auxin gradient. However, the precise roles of the tonoplast proton pumps in gametophyte development remain unclear. Here we demonstrated that the lack of two types of tonoplast proton pumps or the absence of V-ATPase alone leads to abnormal development and nuclear localization of female gametophyte (FG), and slowed endosperm nuclei division after fertilization of the central cell. We further revealed that V-ATPase regulates auxin levels in ovules through coordinating the content and localization of PIN-FORMED 1 (PIN1) protein, hence influencing nuclear spacing between centra cell and egg cell, and subsequent endosperm development. Collectively, our findings revealed a crucial role of V-ATPase in auxin-mediated FG development in Arabidopsis and expanded our understanding of the functions of tonoplast proton pumps in seed plants reproductive development.

Inner limiting membrane peeling prevents secondary epiretinal membrane after vitrectomy for proliferative diabetic retinopathy.

AIM: To evaluate the role of internal limiting membrane (ILM) peeling in preventing secondary epiretinal membrane (ERM) formation in pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: This retrospective study analyzed the medical records of patients who underwent PPV for PDR and were followed up for minimum 3mo. ILM peeling was performed based on the intraoperative surgeons' judgments. ERM was assessed by optical coherence tomography photography. The relationship between ILM peeling and postoperative ERM was analyzed. RESULTS: In total, 212 eyes from 197 patients were included in this study. The incidence of secondary ERM in the ILM non-peeling group was significantly higher than that in the ILM peeling group (37.0% vs 14.0%; P<0.001). Multivariate logistical regression revealed that ILM peeling was highly associated with the prevention of secondary ERM development [odds ratio 0.38; 95% confidence interval 0.17-0.86; P<0.05]. CONCLUSION: ILM peeling during PPV for PDRs can effectively reduce the incidence of secondary ERM development and is worth consideration by vitreoretinal surgeons.

Improved Safety of Hybrid Electroconvulsive Therapy Compared With Standard Electroconvulsive Therapy in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Parallel-Group Pilot Trial.

Objectives: ECT is a rapid and effective treatment for depression. While efficacy is often remarkable over the initial 3-4 sessions, the efficacy of later sessions is less rapid, and the side-effects, especially cognitive impairment limit its use. To preliminarily compare the efficacy and acceptability of a novel hybrid-ECT (HECT) protocol for patients with major depressive disorder (MDD) with standard ECT, we conducted this pilot trial. Methods: Thirty patients were randomly assigned to ECT or HECT. Both arms received three ECT sessions (phase 1) but, in phase 2, the HECT arm received low-charge electrotherapy instead of ECT. The primary outcome was the change in 24-item Hamilton depression rating scale (HAMD-24) scores between baseline and the end of treatment. Cognitive function was assessed by repeatable battery for the assessment of neuropsychological status (RBANS), Stroop color word, and orientation recovery tests (ORT). Safety was measured by the drop-out rate and adverse events (AEs). Four visits were conducted at baseline, post-phase 1, post-phase 2, and at 1-month follow-up. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/), identifier: ChiCTR1900027701. Results: Patients in both arms showed significant within-group improvements in HAMD-24, but the between-group differences were non-significant. Participants in the HECT arm outperformed ECT patients for most cognitive tests at the end of treatment or at follow-up. There was a significantly lower AE rate and shorter ORT in phase 2 of the HECT ar. Conclusion: In this pilot trial, HECT was associated with fewer AEs and better cognitive function including executive and memory function, but its possible similar antidepressive efficacy needs to be further investigated in future.

Prodromal Dementia With Lewy Bodies and Recurrent Panic Attacks as the First Symptom: A Case Report.

Psychiatric-onset dementia with Lewy bodies (DLB) might include symptoms of depression, hallucinations, anxiety, and apathy. Here, we report a patient with DLB with recurrent panic attacks as her first symptom 5 years before a biological-based diagnosis of probable DLB. We provide an extended description of the clinical presentation and course from psychiatric-onset DLB to dementia in an 83-year-old woman. This case illustrates the common misdiagnosis of DLB and the delay of having a detailed clinical and biomarker assessment for structured diagnosis. With a detailed description of the clinical presentation of this case, the empirical treatment strategies, and the patient perspectives, we aim to make clinicians aware of panic attacks within the psychiatric-onset DLB.

PIN3 positively regulates the late initiation of ovule primordia in Arabidopsis thaliana.

Ovule initiation determines the maximum ovule number and has great impact on seed number and yield. However, the regulation of ovule initiation remains largely elusive. We previously reported that most of the ovule primordia initiate asynchronously at floral stage 9 and PINFORMED1 (PIN1) polarization and auxin distribution contributed to this process. Here, we further demonstrate that a small amount of ovule primordia initiate at floral stage 10 when the existing ovules initiated at floral stage 9 start to differentiate. Genetic analysis revealed that the absence of PIN3 function leads to the reduction in pistil size and the lack of late-initiated ovules, suggesting PIN3 promotes the late ovule initiation process and pistil growth. Physiological analysis illustrated that, unlike picloram, exogenous application of NAA can't restore these defective phenotypes, implying that PIN3-mediated polar auxin transport is required for the late ovule initiation and pistil length. qRT-PCR results indicated that the expression of SEEDSTICK (STK) is up-regulated under auxin analogues treatment while is down-regulated in pin3 mutants. Meanwhile, overexpressing STK rescues pin3 phenotypes, suggesting STK participates in PIN3-mediated late ovule initiation possibly by promoting pistil growth. Furthermore, brassinosteroid influences the late ovule initiation through positively regulating PIN3 expression. Collectively, this study demonstrates that PIN3 promotes the late ovule initiation and contributes to the extra ovule number. Our results give important clues for increasing seed number and yield of cruciferous and leguminous crops.

A Preliminary Study of Different Treatment Strategies for Anxious Depression.

BACKGROUND: Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing different treatment methods in patients with anxiety/somatic subtype MDD. AIM: To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD. METHODS: This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment. RESULTS: Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942). CONCLUSION: This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.

Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases.

BACKGROUND: Penfluridol, isolated from an FDA-approved small-molecule drug library as an inhibitor of tumor necrosis factor α (TNFα)-stimulated NF-κB activation, is clinically used to treat chronic schizophrenia and related disorders. This study is aimed to investigate the therapeutic effect of penfluridol on TNFα-stimulated inflammatory autoimmune diseases, particularly inflammatory arthritis. METHODS: Various in vitro studies to confirm the inhibitory effect of penfluridol on TNFα-induced NF-κB activity in bone marrow-derived macrophages or Raw 264.7 macrophage cell line. In vivo studies assessed the therapeutic effects of penfluridol in various disease models, including TNFα transgenic mice, collagen-induced arthritis, DSS-induced colitis, and TNBS-induced colitis. Identification and characterization of the binding of penfluridol to acid sphingomyelinase using bioinformatics and drug affinity responsive target stability assay. Acid sphingomyelinase activity assays to reveal penfluridol-mediated inhibition of acid sphingomyelinase activity. siRNA knockdown experiments to illustrate the dependence of penfluridol's anti-TNF activity on acid sphingomyelinase. RESULTS: Penfluridol effectively inhibited TNFα-induced NF-κB activation in vitro and alleviated the severity of arthritis and colitis in vivo. Mechanistic studies revealed that penfluridol bound to acid sphingomyelinase and inhibited its activation. In addition, knockdown of acid sphingomyelinase largely abolished the inhibitory effects of penfluridol on TNFα-induced inflammatory cytokine production. Furthermore, penfluridol suppressed the differentiation of spleen naive CD4+T cells to TH1 and TH17 and inhibited M1 macrophage polarization. CONCLUSION: This study provides the rationale for the possible innovative use of penfluridol as a newly identified small-molecule drug for TNFα-driven diseases, such as inflammatory arthritis and colitis.

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.

Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy.

Retinal pigment epithelium (RPE) serves critical functions in maintaining retinal homeostasis. An important function of RPE is to degrade the photoreceptor outer segment fragments daily to maintain photoreceptor function and longevity throughout life. An impairment of RPE functions such as metabolic regulation leads to the development of age-related macular degeneration (AMD) and inherited retinal degenerative diseases. As substrate recognition subunit of a ubiquitin ligase complex, suppressor of cytokine signaling 2 (SOCS2) specifically binds to the substrates for ubiquitination and negatively regulates growth hormone signaling. Herein, we explore the role of SOCS2 in the metabolic regulation of autophagy in the RPE cells. SOCS2 knockout mice exhibited the irregular morphological deposits between the RPE and Bruch's membrane. Both in vivo and in vitro experiments showed that RPE cells lacking SOCS2 displayed impaired autophagy, which could be recovered by re-expressing SOCS2. SOCS2 recognizes the ubiquitylated proteins and participates in the formation of autolysosome by binding with autophagy receptors and lysosome-associated membrane protein2 (LAMP-2), thereby regulating the phosphorylation of glycogen synthase kinase 3ß (GSK3ß) and mammalian target of rapamycin (mTOR) during the autophagy process. Our results imply that SOCS2 participates in ubiquitin-autophagy-lysosomal pathway and enhances autophagy by regulating GSK3ß and mTOR. This study provides a potential therapeutic target for AMD.