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This study aimed to explore whether RO4929097 (RO), a specific γ-secretase inhibitor, could inhibit the subretinal fibrosis in laser-induced mouse model and the relevant molecular mechanisms.Male C57BL/6J mice were used to produce choroidal neovascularization (CNV) and subretinal fibrosis by laser photocoagulation, and RO was administered intravitreally 1 day after laser induction. The sizes of CNV and subretinal fibrosis were measured and quantified in both 2D and 3D constructions. The ARPE-19 cell line and primary human RPE (phRPE) cells were treated with TGFβ1, in combination with or without RO, to examine Notch related molecules, epithelial mesenchymal transition (EMT), cell viability, migration, and contractile function, as well as the crosstalk between Notch and other EMT relevant signaling pathways.Intravitreal injection of RO reduced the sizes of both CNV and subretinal fibrosis in laser-induced young and old mice at day 7 and day 14 after laser induction. Moreover, EMT and Notch activation in RPE-choroid complexes from laser-induced mice were significantly attenuated by RO. In vitro, TGFβ1 activated Notch signaling and induced EMT in ARPE-19 cells, accompanied by enhanced EMT-related function, which were inhibited by RO. The inhibition of RO on EMT was further confirmed in TGFβ1-treated phRPE cells. Blockage of Notch signaling by RO could inhibit ERK1/2 signaling; whereas ERK1/2 inhibition had no effect on Notch. The action of RO was independent of Smad2/3 or p38, and co-inhibition of Notch and Smad2/3 showed synergistic effect on EMT inhibition.RO exerts its antifibrotic effect by directly inhibiting Notch signaling and indirectly suppressing ERK1/2 signaling. Targeting Notch signaling might provide a therapeutic strategy in prevention and treatment of subretinal fibrosis in neovascular age-related macular degeneration (nAMD).

Purpose. To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti-VEGF) treatment and its association with the retinal microcapillary density. Methods. Twenty-five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti-VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. Results. The mean interval between baseline and follow-up with OCTA was 93.08 ± 5.00 (range, 85-101) days. Compared with the baseline, the number of HRF significantly decreased in DCP ( 7.52 ± 3.06 vs. 3.76 ± 1.48 , P < 0.01 ) and outer retina ( 12.04 ± 4.91 vs. 5.88 ± 3.32 , P < 0.01 ) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. Conclusion. The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti-VEGF treatment in patients with AMD.

Background Angiogenesis is an important parameter in the development of diabetic retinopathy (DR), and it is indicative of an early stage evolving into a late phase. Therefore, examining the role of angiogenic factors in early DR is crucial to understanding the mechanism of neovascularization. Methods The present study identified hub genes and pathways associated with angiogenesis in early DR using bioinformatics analysis. Genes from published literature and Gene Expression Omnibus (GEO) were collected and analysed. Results We collected 73 genes from 70 published studies in PubMed, which were referred to as DR-related gene set 1 (DRgset1). The gene expression profile of GSE12610 was downloaded, and 578 differentially expressed genes (DEGs) between diabetic and normal samples were identified. DEGs and DRgset1 were further combined to create DR-related gene set 2 (DRgset2). After an enrichment analysis, we identified 12 GO terms and 2 pathways associated with neovascularization in DRgset1, and 8 GO terms and 2 pathways in DRgset2. We found 39 new genes associated with angiogenesis and verified 8 candidate angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1. We identified 10 hub genes associated with neovascularization by constructing a protein-protein interaction (PPI) network: TNF, VEGFA, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1. Conclusions The present study analysed angiogenesis-related genes and pathways in early DR in a comprehensive and systematic manner. PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1 may be the candidate genes to further explore the mechanisms of angiogenesis in early DR. TNF, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1 may be new targets for early neovascularization therapy in the future.

Introduction: We characterized the role of aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) in retinal inflammation and apoptosis regulation, both in vivo and in vitro. In addition, we used clinical specimens to show the relationship between AIMP1 and the development of diabetic retinopathy (DR). Objective: To elucidate the role of AIMP1 in DR. Methods: A diabetic AIMP1-specific knockout (KO) C57 mouse model was used. Human retinal microvascular endothelial cells (HRMECs) were incubated with normal glucose, high glucose (HG), and HG + AIMP1-small interfering RNA (siRNA). The expression of AIMP1 and relative inflammatory and apoptotic cytokines in diabetic mice retina and HRMECs were measured using Western blotting and polymerase chain reaction. The apoptosis of HRMECs was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The levels of AIMP1 in the vitreous humor and serum were determined using ELISA. Possible correlations between the intravitreal level of AIMP1 and blood glucose, glycosylated hemoglobin HbA1c, intravitreal levels of IL-1β, and caspase-3 were determined. Results: The expression of inflammatory and apoptotic proteins was inhibited in the AIMP1 KO mice and HRMECs incubated with AIMP1-siRNA. The apoptosis of HRMECs was decreased in the AIMP1-siRNA group. The intravitreal level of AIMP1 in DR patients was significantly higher than that in nondiabetic patients (p < 0.01). There was a positive correlation between intravitreal AIMP1 and HbA1c and intravitreal IL-1β and caspase-3 (p < 0.05). Conclusions: HG induced increased expression of AIMP1 in HRMECs and retinas from diabetic C57 mice, thereby increasing the expression of inflammatory and apoptotic cytokines, which promoted DR progression. A decrease in AIMP1 expression prevented the development of DR by inhibiting the activation of inflammatory and apoptotic signaling. Therefore, AIMP1 is an effective interfering target for the prevention and treatment of DR.

Diabetic retinopathy (DR) is prevalent among people with long-term diabetes mellitus (DM) and remains the leading cause of visual impairment in working-aged people. DR is related to chronic low-level inflammatory reactions. Pyroptosis is an emerging type of inflammatory cell death mediated by gasdermin D (GSDMD), NOD-like receptors and inflammatory caspases that promote interleukin-1β (IL-1β) and IL-18 release. In addition, the retinal neurovascular unit (NVU) is the functional basis of the retina. Recent studies have shown that pyroptosis may participate in the destruction of retinal NVU cells in simulated hyperglycemic DR environments. In this review, we will clarify the importance of pyroptosis in the retinal NVU during the development of DR.

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

Microvascular dysfunction is the primary aetiology of visual impairment caused by diabetic retinopathy (DR). Dihydroartemisinin (DHA), the active metabolite of the antimalarials artemisinins, exhibits antiangiogenic properties in numerous diseases. Here, we investigated the function and mechanisms of DHA as a vasculoprotective agent in DR. DHA exerted its protective effect on vascular injuries in diabetic mice and inhibited cell proliferation and tube formation in human retinal microvascular endothelial cells by decreasing the level of fatty acid synthase (FASN), enhancing the malonylation of mechanistic target of rapamycin (mTOR) at lysine 1218 (K1218) and attenuating the activation of mTOR complex 1 (mTORC1). Impressively, a chemosynthetic small interfering RNA against FASN and mutagenesis of K1218 of mTOR showed therapeutic potential in suppressing cell proliferation and tube formation induced by high glucose. Notably, suppression of mTORC1 kinase activity further inhibited FASN by reducing p70S6K phosphorylation to subsequently reduce the expression of sterol regulatory element binding protein 1, which interacted directly with the FASN promoter at nucleotide positions −64 and −55. In conclusion, our study elucidated the promising effects of FASN and malonylation on vascular injuries of DR and indicated the great potential of DHA as a therapeutic approach.

Immune thrombocytopenia is a common complication in patients in a minimally conscious state (MCS). MCS patients are prone to pulmonary infection for the reasons of long-term bed rest and tracheotomy etc., which leads to frequent immune thrombocytopenia. At present, there is no specific treatment for immune thrombocytopenia. Moreover, the cost of routine treatment is high, and clinicians need to consider different drug combinations, side effects, and the risk of drug dependence when selecting treatments. Here, we report a case of a patient in a MCS who developed immune thrombocytopenia after tracheotomy and long-term bed laying in October 2015. The patient's platelet count declined continuously, and by December 2015, she was in a critical condition, with a platelet count of less than 20×109/L. The patient firstly received routine treatment, however, this could only temporarily prevent the drop in platelets. Following a series of explorations, the patient was treated with a combination of traditional Chinese and Western medicine, which included treatment and preventive measures. For treatment, the patient was given roxithromycin dispersible administration tablets and a self-made preparation of peanut red skin, which could quickly cure the immune thrombocytopenia. Preventive measures included the addition of ursodeoxycholic acid capsules, silybin capsules, and a traditional Chinese medicine preparation. As shown by laboratory examination results, the patient's platelet count has stayed around a normal level since March 2016, and she now has normal liver and kidney function. This outcome evidence that combined traditional Chinese and Western medicine could effectively cure immune thrombocytopenia and prevent its recurrence. Moreover, the cost of the treatment was lower and there were fewer side effects than routine treatment, and at the same time, the method of treatment was simple and convenient. Our practical experience may provide a valuable clue for the treatment of immune thrombocytopenia.

High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.

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

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-1β, 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-1β 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-1β-mediated positive feedback loop.

The purpose of this study is to compare the efficacy of intraoperative 360° and localized laser retinopexy in 23-gauge pars plana vitrectomy (PPV) for rhegmatogenous retinal detachments (RRD) with undetected retinal breaks intraoperatively. This is a retrospective, comparative, interventional study. Medical records of 48 consecutive eyes with RRD of intraoperative undetected retinal breaks were reviewed. Nineteen patients (group I) received 360° laser retinopexy in PPV, while the remaining 29 patients (group II) underwent localized laser retinopexy. In group I, a triple row of confluent medium-white laser burns were placed posterior to the ora serrata. Anatomical and visual outcomes of the two groups were compared. The mean follow-up period was 13.46 ± 3.02 months. No significant difference was identified in baseline characteristics. A single-operation reattachment rate of 89.47% was achieved in group I, which was significantly higher than that of group II (55.17%, p = 0.01), and this trend was not weakened after adjustment for the confounding factor (odds ratio 0.15, p = 0.03). Moreover, greater improvement of postoperative best-corrected visual acuity was observed in group I. Significant complications sufficient to require further operation included proliferative vitreoretinopathy in 2 (4.17%) eyes and epiretinal membrane in 4 (8.33%) eyes. Three hundred sixty-degree laser retinopexy was associated with better anatomic and visual outcomes in RRD patients with unseen breaks intraoperatively, when compared with localized laser retinopexy in PPV.

Backgrounds. Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. Methods. C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. Results. OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. Conclusions. We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD.

Background Ocular fundus angiography is an indispensable component of the tests utilized for fundus diseases. Dynamic angiography results can provide additional information; however, many difficulties remain. In this study, we introduce a modified method, time-lapse angiography (TLA), to dynamically present imaging results. Methods TLA, combining time-lapse photography and fundus angiography (using Heidelberg retina angiography II, Germany), includes pre-photographing and post- photosynthesis and ultimately produces a video that is approximately 15 s in length. Results Four typical videos in the article showed the characteristics of TLA, including a short and rapid but continuous and integral presentation, highly valid information, high definition, etc. Conclusions TLA is beneficial for the diagnosis of diseases and the assessment of progression and is convenient for peer communication, patient interpretation, and student education. The application of time-lapse photography in ocular fundus angiography is a monumental and innovative attempt.

Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss worldwide, with an annual incidence rate of 6.3 to 18.9 per 100,000 individuals.1–3 The main treatment modality for RRD is surgical reattachment of the retina, which includes pneumatic retinopexy (PR), scleral buckling (SB), and vitrectomy. Generally, vitrectomy is indicated for relatively complicated RRD.4 However, vitrectomy may be more frequently associated with cataract aggravation, secondary glaucoma, and a high economic burden to poor patients in developing countries.5–7 PR has long been used for the management of RRD because it is convenient and less invasive.8–11 SB cures RRD by releasing vitreous traction, closing the retinal breaks, and bringing the retina and retinal pigment epithelium (RPE) closer to each other.12 Both PR and SB preserve the vitreous. However, they are usually indicated for relatively simple RRD. Prior studies have indicated that low intraocular pressure (IOP), persistent intraoperative detachment at the buckle, macular-off status, and posterior retinal breaks are risk factors for surgical failure of SB.13–15 Meanwhile, inferior breaks and visible vitreous traction on a tear often predict failure of PR.16,17 Nonetheless, PR and SB can complement each other. Early in 1985, Gilbert and McLeod18 and Stanford and Chignell19 introduced a technique involving sequential subretinal fluid (SRF) drainage (D), intravitreal injection of air (A), trans-scleral cryopexy (C), and episcleral explant (E) (DACE) for selected patients with bullous retinal detachment (RD). The primary operation success rates were 90%18 and 96%,19 respectively. However, after including more complicated cases (e.g., RRD with unseen retinal breaks, macular holes [MHs], or some degree of proliferative vitreoretinopathy [PVR]), the single-operation success rate decreased to 67%.20 Even after reoperation, the reattachment rate was only 81%.20 In a subsequent study, Cheng et al.21 performed short-term external SB combined with PR in patients with RRD with inferior breaks and reported a single-operation reattachment rate of 87.9%. Consistent with our clinical experience, a single PR with external drainage of SRF rarely achieves complete retinal reattachment in relatively complicated RRD because of the deep SRF, static vitreoretinal tractions on a tear, and deep locations of retinal breaks. The use of a small gas bubble in prior studies was largely ineffective for complete release of the vitreoretinal traction. In the past few years, maximal PR has been developed in our practice. Maximal PR involves injection of an adequately large non-expansile gas bubble into the vitreous to achieve thorough release of the vitreoretinal traction. We have performed maximal PR and SRF drainage combined with SB for treatment of relatively complicated RRD, such as those involving tractional tears, vitreous hemorrhage, unseen retinal breaks, and posterior holes (including MHs) with combined peripheral retinal breaks, and favorable results were achieved. The purpose of the present study was to introduce and evaluate the efficacy of maximal PR and SRF drainage together with SB for the management of relatively complicated RRD.

The aim of this systematic review was to determine the anatomical outcome—macular hole (MH) closure rate—and functional outcome—visual acuity (VA) improvement rate—of the inverted internal limiting membrane (ILM) flap technique for large MH. We searched for articles on large MH (> 400 μm) treated with inverted ILM flap technique in databases as of December 1, 2017. And single-arm meta-analysis was performed for the primary outcome of MH closure rate and the secondary outcome of VA improvement rate. In addition, we searched and pooled studies treating large MH with indocyanine green (ICG)-assisted ILM peeling as the reference. R software (version 2.15.2) was used for analysis. This review includes eight studies that used inverted ILM flap technique to treat large MH (> 400 μm). Based on the single-arm meta-analysis performed in R 2.15.2, the pooled MH closure rate and VA improvement rate following inverted ILM flap technique were 95% (95% CI, 88 to 98%) and 75% (95% CI, 62 to 85%), respectively, in fixed-effect models. There was no substantial methodological heterogeneity. In addition, we selected four studies on large MH treated with ICG-assisted ILM peeling as the reference. The fixed-model pooled MH closure rate and VA improvement rate were 87% (95% CI, 79 to 92%) and 57% (95% CI, 46 to 68%), respectively. Inverted ILM flap technique should be an effective and safe method for treating large MH, with high closure rates and good VA improvement. However, further studies in large randomized controlled trials on minimizing surgical complications and understanding the mechanism of this technique are necessary.

To compare the efficacy of air and octafluoropropane (C3F8) in treating rhegmatogenous retinal detachments with inferior breaks after 23-gauge pars plana vitrectomy.A prospective, randomized comparative interventional study. Sixty-four patients with rhegmatogenous retinal detachment with inferior breaks underwent pars plana vitrectomy with air (32 eyes) or gas (32 eyes) tamponade. Anatomical and visual outcomes of the two groups were compared.The mean follow-up period was 13.09 ± 1.90 months. Significant differences were identified regarding prone positioning period (P0.01), intraocular pressure (P0.01), and gas volume (P = 0.03) on the first postoperative day. The single-operation success rates for the air and gas groups were 84.38% and 78.13% (P = 0.522), and the final surgery success rates increased to 100% and 96.88% (P = 0.313), respectively. The single-operation success rate between the groups was not statistically significant, even after adjustment for confounding factors. Multivariate logistic regression also indicated that the number of involved retinal quadrants (odds ratio = 19.88, P = 0.01) was an independent predictor of surgery failure. The only postoperative complication observed was new or missed breaks, which occurred in 12 patients (18.75%).Air had equivalent tamponade effects to C3F8, with a shorter prone positioning period, fewer complications, and less expense, in the surgical management of rhegmatogenous retinal detachment with inferior breaks.

Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS–TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Recurrent retinal detachment (RD) in silicone oil-filled eyes is a serious condition. At the initial stage, it usually spares the macular and is localized in the inferior retina. The inability to locate the retinal breaks has been reported to be associated with a poor prognosis and has limited the use of conventional vitreoretinal surgeries. Demarcation laser photocoagulation (DLP) is widely accepted for treating macular-sparing RDs. For laser treatments to be effective, an adequate extent and the correct placement of the laser is of great importance. The purpose of this research was to compare the efficacy of 360° and localized DLP in the management of macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks.This is a retrospective, comparative, interventional study. The medical records of 48 consecutive eyes with macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks were reviewed. Twenty-six patients (group I) received 360° DLP, and the remaining 22 patients (group II) underwent localized DLP. The anatomical and visual outcomes of the two groups were compared.The mean follow-up period was 12.54 ± 1.17 months. No significant difference was identified in the baseline characteristics. The single-operation success rate of 92.31% was achieved in group I, which was significantly higher than that of group II (59.09%, P = 0.01), and this trend was not weakened after adjusting for confounding factors (odds ratio: 0.002, P = 0.02). After salvage management of vitreoretinal surgeries, both groups had equivalent visual outcomes with silicone oil removal. Multivariate logistic regression also indicated that the radial extent of RD (odds ratio: 11.10, P = 0.04) was an independent predictor for laser treatment failure. Significant complications sufficient to require further operations included proliferative vitreoretinopathy in two (4.17%) eyes and epiretinal membrane in four (8.33%) eyes.The 360° DLP achieved a better primary success rate and equivalent visual outcomes with localized DLP for macular-sparing RD in silicone oil-filled eyes with no detected retinal breaks.

The mechanisms underlying the cellular metabolic memory induced by high glucose remain unclear. Here, we sought to determine the effects of microRNAs (miRNAs) on metabolic memory in diabetic retinopathy. The miRNA microarray was used to examine human retinal endothelial cells (HRECs) following exposure to normal glucose (N) or high glucose (H) for 1 week or transient H for 2 days followed by N for another 5 days (H→N). Levels of sirtuin 1 (SIRT1) and acetylated-nuclear factor κB (Ac-NF-κB) were examined following transfection with miR-23b-3p inhibitor or with SIRT1 small interfering (si)RNA in the H→N group, and the apoptotic HRECs were determined by flow cytometry. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of miR-23b-3p inhibitor. Chromatin immunoprecipitation (ChIP) analysis was performed to detect binding of NF-κB p65 to the potential binding site of the miR-23b-27b-24-1 gene promoter in HRECs. High glucose increased miR-23b-3p expression, even after the return to normal glucose. Luciferase assays identified SIRT1 as a target mRNA of miR-23b-3p. Reduced miR-23b-3p expression inhibited Ac-NF-κB expression by rescuing SIRT1 expression and also relieved the effect of metabolic memory induced by high glucose in HRECs. The results were confirmed in the retina using a diabetic rat model of metabolic memory. High glucose facilitated the recruitment of NF-κB p65 and promoted transcription of the miR-23b-27b-24-1 gene, which can be suppressed by decreasing miR-23b-3p expression. These studies identify a novel mechanism whereby miR-23b-3p regulates high-glucose-induced cellular metabolic memory in diabetic retinopathy through a SIRT1-dependent signalling pathway.

We used flash electroretinography (F-ERG) to determine if retinal function was impaired in patients with hyperlipidemia, including visual acuity and fundus morphological changes, and to identify predictors of impaired retinal function in hyperlipidemia patients.This was a prospective case-control study (Shanghai, China; February 2011 to January 2012) in 696 hyperlipidemia patients and 136 healthy controls. Exclusion criteria included best-corrected visual acuity0.6, previous intraocular surgery, and chronic comorbidities. Each participant underwent a comprehensive series of ophthalmologic examinations, and standard F-ERG examination. Data were analyzed using t-tests and multivariate analysis.Six hundred and twenty-six hyperlipidemia patients (57.69 ± 14.01 years; 59.58% female) and 120 healthy controls (55.13 ± 14.03 years; 60% female) were included in the final analysis. After adjustment for age and gender using multivariate covariance analysis, F-ERG result revealed significantly lower response amplitudes in the hyperlipidemia group (P 0.05), and longer implicit times (P 0.05) than the control group. F-ERG parameters were significantly different between the two groups. Stepwise multiple linear regression analysis showed that serum LDL levels (P 0.001), BMI (P 0.001), duration of hyperlipidemia (P 0.001), and serum HDL levels (P = 0.03) were negatively correlated with ΣOps.The present study suggests that the retinal function of hyperlipidemia patients was significantly lower than in healthy controls, even before the occurrence of pathological changes in the fundus.