Selectively targeting disease-restricted secretogranin III to alleviate choroidal neovascularization.

Choroidal neovascularization (CNV), a leading cause of blindness in the elderly, is routinely treated with vascular endothelial growth factor (VEGF) inhibitors that have limited efficacy and potentially adverse side effects. An unmet clinical need is to develop novel therapies against other angiogenic factors for alternative or combination treatment to improve efficacy and safety. We recently described secretogranin III (Scg3) as a disease-selective angiogenic factor, causally linked to diabetic retinopathy and acting independently of the VEGF pathway. An important question is whether such a disease-selective Scg3 pathway contributes to other states of pathological angiogenesis beyond diabetic retinopathy. By applying a novel in vivo endothelial ligand binding assay, we found that the binding of Scg3 to CNV vessels in live mice was markedly increased over background binding to healthy choriocapillaris and blocked by an Scg3-neutralizing antibody, whereas VEGF showed no such differential binding. Intravitreal injection of anti-Scg3 humanized antibody Fab (hFab) inhibited Matrigel-induced CNV with similar efficacy to the anti-VEGF drug aflibercept. Importantly, a combination of anti-Scg3 hFab and aflibercept synergistically alleviated CNV. Homozygous deletion of the Scg3 gene markedly reduced CNV severity and abolished the therapeutic activity of anti-Scg3 hFab, but not aflibercept, suggesting a role for Scg3 in VEGF-independent CNV pathogenesis and therapy. Our work demonstrates the stringent disease selectivity of Scg3 binding and positions anti-Scg3 hFab as a next-generation disease-targeted anti-angiogenic therapy for CNV.

The association between circulating neutrophil extracellular trap related biomarkers and retinal vein occlusion incidence: A case-control pilot study.

Retinal vein occlusion (RVO) is the second most common retinal vascular disorders and causes visual damage in a large population. Neutrophil extracellular traps (NETs) formation (NETosis) is an important cause of vascular diseases, however, the association between NETs related biomarkers and RVO development remained unclear. In this pilot study, a total of 77 RVO cases and 48 controls were included between Jan 2020 and July 2020. Besides, the circulating levels of three NETs related markers, cell-free DNA (cfDNA), myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit), were detected in all the participants and thus the association between NETosis and RVO incidence was analyzed. Advanced assays were conducted to investigate the inflammation and thrombosis related biomarkers in RVO cases with higher or lower NETs biomarkers. When the results were considered, it was found that NETs biomarkers, including cfDNA, MPO-DNA and H3Cit, were increased in the RVO cases comparing with the controls (P < 0.05). Through the receiver operating characteristic (ROC) analyses, we found that circulating NETs related biomarkers demonstrated potential diagnostic effects for RVO and the AUCs of plasma cfDNA, MPO-DNA and H3Cit were 0.859, 0.871 and 0.928, respectively (P < 0.001). Through analyzing the correlations between circulating NETs markers and RVO stages and durations, inflammatory markers as well as thrombotic indexes, it was found that NETs were related with the RVO subtypes, inflammatory status and thrombus formation. In conclusion, the plasma NETs remnants are significantly increased in RVO cases. Besides, advanced studies demonstrate that inflammation as well as thrombus formation might be involved in this association.

The Neurovascular Protective Effect of S14G-Humanin in a Murine MCAO Model and Brain Endothelial Cells.

Endothelial dysfunction is fundamental to ischemic stroke and brain injury. The humanin analogue S14G-humanin (HNG) has been shown to be a cytoprotective derivative. In this study, we investigated the neuroprotective effects of HNG in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, HNG ameliorates cerebral infarction and suppresses the production of TNF-α, IL-1ß, IL-6 and MCP-1 cytokines. HNG inhibits the expression of vascular adhesion molecules such as VCAM-1 and ICAM-1 in the cortex tissue. In mouse brain endothelial cells bEnd.3, HNG protects cell survival under oxygen deprivation (OGD) conditions. HNG suppresses ROS production as well as that of the same panel of cytokines and vascular adhesion molecules induced by OGD. HNG also reduces the numbers of THP-1 cells attached to bEnd.3 by OGD. Mechanistically, we show that HNG exerts its effect via inhibition of the NF- κB pathway factor IKKα, activation of IκBα and accumulation of p65 in the nucleus. Our data conclude that S14G-humanin serves as a neuroprotective factor, especially in brain vascular disorders. © 2018 IUBMB Life, 70(7):691-699, 2018.

Comparative ligandomics implicates secretogranin III as a disease-restricted angiogenic factor in laser-induced choroidal neovascularization.

Choroidal neovascularization (CNV) is a leading cause of vision loss in the elderly. All approved anti-angiogenic drug therapies for CNV target vascular endothelial growth factor (VEGF) but confer limited efficacy. Identification of other CNV-related angiogenic factors will facilitate the development of VEGF-independent alternative therapies. Here, we applied comparative ligandomics to live mice with or without laser-induced CNV for global mapping of CNV-selective endothelial ligands. Secretogranin III (Scg3) previously identified by the same approach as a diabetes-restricted angiogenic factor was mapped with a more than 935-fold increase in binding to CNV vessels compared to healthy choriocapillaris. A novel in vivo ligand binding assay independently confirmed a marked increase in Scg3 binding to CNV vessels, whereas VEGF showed no increase in CNV-selective binding. A new technique of functional immunohistochemistry allowed the visualization and confirmed the increase in in vivo Scg3 binding to CNV vasculatures, including CNV microcapillaries with detailed vascular structures, which was blocked by anti-Scg3 humanized antibody Fab fragment (hFab). The hFab effectively alleviated laser-induced CNV with an efficacy similar to the anti-VEGF drug aflibercept. Homozygous deletion of the Scg3 gene in mice significantly reduced the severity of CNV. Furthermore, the therapeutic activity of anti-Scg3 hFab, but not aflibercept, was abolished in Scg3-/- mice, suggesting the Scg3-dependent nature of the hFab-mediated therapy. These findings suggest that Scg3 plays an important role in CNV pathogenesis and is a promising disease-restricted angiogenic factor for ligand-guided disease-targeted anti-angiogenic therapy of CNV.

Protective Role of microRNA-200a in Diabetic Retinopathy Through Downregulation of PDLIM1.

BACKGROUND: Diabetic retinopathy (DR) is a most common microvascular complication and regarded as the leading cause of blindness in the working age population. The involvement of miR-200a in various disorders has become recognized, and the objective of this study was to identify the protective effect of miR-200a in the development of DR. METHODS: The contents of miR-200a and its potential target gene, PDZ and LIM domain protein 1 (PDLIM1), were detected in both in-vivo and in-vitro DR models. Retinal leakage and inflammatory factor concentrations were detected after vitreous injections of miR-200a/PDLIM1 vectors in mice. The cellular viability, apoptosis and cellular migration were investigated using trypan blue staining, flow cytometry and transwell assay with human retinal microvascular endothelial cells (HRMECs). Besides, the prediction and confirmation of miR-200a targeting PDLIM1 were conducted with bioinformation analyses and dual-luciferase reporter assay. RESULTS: Lower miR-200a and higher PDLIM1 levels were detected in both in-vivo and in-vitro DR models. Besides, it was found that miR-200a treatment would significantly inhibit retinal permeability and inflammatory factors. Through targeting PDLIM1, it was found that miR-200a could improve cellular viability, remit apoptotic status and reduce cellular migration significantly in high glucose-treated HRMECs. CONCLUSION: Our results demonstrated that miR-200a could be used as a potential therapy target through down-regulating PDLIM1 in DR.

Asiatic acid attenuates diabetic retinopathy through TLR4/MyD88/NF-κB p65 mediated modulation of microglia polarization.

AIM: This study aimed to evaluate the effects of Asiatic acid (AA), a naturally occurring compound of pentacyclic triterpenoid, on the pathological processes of diabetic retinopathy (DR). METHODS: SD rats were induced to develop early DR by intraperitoneal injection of STZ (60 mg/kg). Four weeks after injection, the diabetic rats were orally administrated with 37.5 mg/kg or 75 mg/kg AA every day for four weeks. The integrity of blood-retinal barrier (BRB) was measured by Evans blue staining. The polarization of microglia was determined by real-time PCR, western blot, and ELISA assays. The inner BRB (iBRB) or outer BRB (oBRB) breakdown was induced in human retinal endothelial cells or APRE19 cells through co-culture with high glucose and LPS-stimulated microglia BV2 cells. The damage to the iBRB and oBRB was measured using transendothelial/transepithelial electrical resistance (TEER/TER) and FITC-conjugated dextran cell permeability assays. KEY FINDINGS: Results demonstrated that AA alleviated BRB breakdown, as evidenced by decreased protein expression of occludin, claudin-5, and ZO-1. Furthermore, AA treatment suppressed inflammation and M1 polarization, while it increased M2 polarization in the retina of DR rats. In vitro, the iBRB or oBRB breakdown was alleviated by AA. LPS-induced M1-polarization of BV2 cells under high glucose condition was also repressed through AA administration. Finally, we demonstrated that AA weakened the TLR4/MyD88/NF-κB p65 signaling pathway both in vivo and in vitro. SIGNIFICANCE: AA ameliorated early DR by regulating microglia polarization via the TLR4/MyD88/NF-κB p65 pathway. These data indicate that AA is a potential candidate for DR treatment.

Obstructive Sleep Apnea is Related with the Risk of Retinal Vein Occlusion.

BACKGROUND: Retinal vein occlusion (RVO) was a vision-threatening retinal vascular disorder, however, the relationship between obstructive sleep apnea (OSA) and RVO risk remained unclear. METHODS: A total of 45 RVO cases and 45 controls between April 2018 and April 2020 were included. All the participants underwent full-night polysomnography (PSG) and thus detected the severity of OSA. Besides, the relationship between the apnea-hypopnea index (AHI) and oxidative and inflammatory biomarkers, including 8-hydroxy-2 deoxyguanosine (8-OHdG), C-reactive protein (CRP), interleukin 1 beta (IL1ß), interleukin 6 (IL6) and tumor necrosis factor alpha (TNFα) were detected. The incidences of macular edema (ME) and neovascular glaucoma (NVG) were detected in a three-months follow-up. RESULTS: In this case-control study, it was found that OSA incidence was increased in the RVO cases comparing with the cataract controls. Advanced analyses about the RVO subtypes demonstrated that incidence of OSA was higher in the central RVO (CRVO) cases comparing with branch RVO (BRVO) cases. Plasma samples from OSA cases demonstrated relatively higher concentrations of oxidative stress parameters and inflammatory biomarkers, including 8-OHdG, CRP, IL1ß, and IL6, in the RVO cases. Significant linear correlations between AHI and oxidative/inflammatory biomarkers were detected, and advanced analyses on the OSA subtypes demonstrated that these biomarkers were significantly higher in cases with later stages of OSA. In a three months follow-up, an impaired visual activity improvement rate and increased ME incidence in the OSA group among all the RVO cases were detected. CONCLUSION: OSA was related with an increased incidence of RVO. Besides, OSA would lead to increased oxidative and inflammatory biomarkers concentrations in the RVO cases. OSA could be used as a harmful prognostic factor of visual activity improvement and ME incidences. These findings highlighted the role of OSA in the development of RVO.

Grape Seed Proanthocyanidin Extract Moderated Retinal Pigment Epithelium Cellular Senescence Through NAMPT/SIRT1/NLRP3 Pathway.

BACKGROUND: Retinal pigment epithelium (RPE) cellular senescence is an important process in degenerative retinal disorders. Grape seed proanthocyanidin extract (GSPE) alleviates senescence-related degenerative disorders; however, the potential effects of GSPE intake on RPE cellular senescence through regulating NAMPT/SIRT1/NLRP3 pathway remain unclear. METHODS: The effects of GSPE on NAMPT expression and NAD+ contents were detected with Western blot and assay kit in both in-vivo and in-vitro AMD models. Senescence-related biomarkers, including p16, p21 expressions and ß-gal staining, were conducted in different groups. The protective effects of GSPE treatment on the mitochondrial homeostasis and barrier function of RPE cells were detected using mtDNA lesions analyses, JC-1 staining, ZO1 staining and trans-epithelial cell resistance (TEER) detection. The expression of senescence-associated secretory phenotype (SASP) in different groups would be conducted with qPCR. To demonstrate the potential effects of NAMPT/SIRT1/NLRP3 pathway after GSPE treatment, the protein levels of relevant key regulators after applications of NAMPT inhibitor, Fk866, and SIRT1 inhibitor, EX-527. RESULTS: GSPE significantly improves the NAMPT expression and NAD+ content in aging mice, and thus alleviates the RPE cellular senescence. In advanced in-vitro studies, GSPE significantly up-regulated NAMPT content and thus relieved H2O2 induced NAD+ depression through analyzing the NAD+ contents in different groups. In advanced analyses, it was reported that GSPE could alleviate mitochondrial permeability, mtDNA damage, ZO1 expression and SASP levels in aging RPE cells. Thus, GSPE treatment significantly decreased senescence-related protein p16 and p21, as well as SASP levels in in-vitro aging model, and it was demonstrated that GSPE could illustrate a significant anti-aging effect. The Western blot data in GSPE treatment of aging RPE cells demonstrated that GSPE could significantly improve NAMPT and SIRT1 levels, and thus depressed NLRP3 expression. CONCLUSION: This study indicated that GSPE alleviated RPE cellular senescence through NAMPT/SIRT1/NLRP3 pathway. This study highlighted the potential effects of GSPE on degenerative retinopathy through the crosstalk of NAD+ metabolism, SIRT1 function and NLRP3 activation.

Plasma melatonin levels in patients with diabetic retinopathy secondary to type 2 diabetes.

BACKGROUND: Melatonin is reported to be related to diabetes mellitus (DM) risk; however, the effect of melatonin on diabetic retinopathy (DR) risk remains unclear. AIM: The aim of this study was to determine the effect of melatonin on DR risk. METHODS: A hospital-based case-control study was conducted from January 2020 to June 2020. DR was assessed using the Diabetic Retinopathy preferred practice pattern (PPP)-updated 2019 criteria. The participants were divided into the DM cases without DR (NDR) group, non-proliferative DR (NPDR) group and proliferative DR (PDR) group. Plasma melatonin concentration was detected with the enzyme-linked immunosorbent assay kit. The relationship between plasma melatonin concentration and DR risk as well as severity was assessed. RESULTS: It was found that plasma melatonin was 72.83 ± 16.25, 60.38 ± 13.43, 44.48 ± 10.30 and 44.69 ± 8.95 pg/mL in healthy controls, NDR group, NPDR and PDR group, respectively. In addition, it was found that plasma melatonin could be used as a potential diagnostic biomarker for DR (AUC = 0.893, P < 0.001). There was a significant positive relationship between total bilirubin and melatonin content (P < 0.001) based on the correlation assay. Significant associations between total bilirubin and melatonin content were also detected in the NPDR (R 2 = 0.360, P < 0.001) and PDR (R 2 = 0.183, P < 0.001) groups. CONCLUSION: The data obtained in this study demonstrated that plasma melatonin concen-tration was decreased in DR cases and could be used as a sensitive and specific marker for the diagnosis of DR. A significant positive relationship between total bilirubin and melatonin was detected. More related studies are required to understand the role of melatonin in DR.

Physcion 8-O-ß-glucopyranoside exerts protective roles in high glucose-induced diabetic retinopathy via regulating lncRNA NORAD/miR-125/STAT3 signalling.

Diabetic retinopathy (DR) is the leading cause of decreased vision and blindness globally. The aim of this study was to understand the role of physcion 8-O-ß-glucopyranoside (PG) in high glucose (HG)-induced DR and to investigate whether lncRNA NORAD/miR-125/STAT3 signalling was the underlying mechanism involved in DR. To this end, the serum levels of NORAD, miR-125, and STAT3 were determined in patients with DR. The APRE-19 cells were subjected to HG treatment to construct the cell model of DR. HG-disposed APRE-19 cell injury was assessed by detecting cell viability, apoptosis, concentrations of pro-inflammatory cytokines including TNF-α and IL-1ß, and ROS generation. Moreover, the effect of PG on HG-disposed APRE-19 cell injury was investigated. NORAD was then overexpressed to investigate the combined effects of NORAD overexpression and PG on HG-disposed APRE-19 cell injury. Furthermore, the regulatory relationship between NORAD and miR-125 as well as miR-125 and STAT3 was investigated. The expression levels of NORAD and STAT3 were significantly increased in the serum of DR patients, while the miR-125 expression was decreased. The HG treatment-induced injury to APRE-19 cells, which were alleviated by PG treatment. Moreover, PG alleviated HG-disposed injury to ARPE-19 cells by decreasing NORAD. NORAD negatively regulated miR-125 expression and the combined effects of NORAD and PG on HG-disposed ARPE-19 cell injury were reversed by miR-125 overexpression. Furthermore, STAT3 was confirmed as a target gene of miR-125. Our results show that PG exerts protective roles in HG-disposed DR via regulating lncRNA NORAD/miR-125/STAT3 signalling. NORAD/miR-125/STAT3 axis may provide a novel perspective for target therapy of DR.

MiR-25-3p promotes malignant phenotypes of retinoblastoma by regulating PTEN/Akt pathway.

Aberrant expression of microRNAs plays an important role in the pathogenesis and progression of retinoblastoma. MiR-25, a member of the miR-106b˜25 cluster, has been reported to be abnormally expressed in retinoblastoma, but the exact role of it remains unclear. In our study, we found that miR-25-3p was upregulated in retinoblastoma tissues and cell lines. Enforced expression of miR-25-3p in retinoblastoma cell line WERI-RB-1 increased cell growth, colony formation, anchorage-independent growth, cell migration and invasion in vitro and tumor xenograft growth in vivo. In contrast, inhibited miR-25-3p expression in retinoblastoma cell line Y79 suppressed cell growth, colony formation, anchorage-independent growth, cell migration and invasion. Through luciferase reporter assay, we found that phosphatase and tensin homolog (PTEN) was a direct target of miR-25-3p. This was verified by western blot that miR-25-3p overexpression suppressed PTEN and activated Akt signaling. In addition, miR-25-3p was found to promote epithelial-mesenchymal transition (EMT) of WERI-RB-1 cells through PTEN/Akt pathway. Western blot analysis revealed that miR-25-3p overexpression increased Vimentin and Snail expression, and suppressed E-cadherin expression, but this could be reversed by restoring PTEN. Moreover, LY294002 treatment or restoring PTEN expression abolished the effects of miR-25-3p on cell invasion, colony formation and anchorage-independent growth in vitro and tumor xenograft growth in vivo. Taken together, our results suggested that miR-25-3p promotes malignant transformation of retinoblastoma cells by suppressing PTEN.

Long noncoding RNA HAGLROS regulates apoptosis and autophagy in Parkinson's disease via regulating miR-100/ATG10 axis and PI3K/Akt/mTOR pathway activation.

Parkinson's disease (PD) is a common age-related neurodegenerative disease resulted from the progressive degeneration of dopaminergic neurons in the pars compacta region of substantia nigra. The goal of this study was to investigate the effects and mechanisms of long noncoding RNA (lncRNA) HAGLROS on the apoptosis and autophagy in PD. The MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cell model were established, and the expression levels of HAGLROS and miR-100 were determined. Subsequently, the effects of suppression of HAGLROS on apoptosis and autophagy in MPTP-induced PD mouse model and in MPP+-intoxicated SH-SY5Y cells were investigated. In addition, the association between HAGLROS and miR-100 as well as HAGLROS and activation of phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in MPP+-intoxicated SH-SY5Y cells was explored. HAGLROS was increasingly expressed in MPTP-induced PD mouse model and MPP+-intoxicated SH-SY5Y cells and suppression of HAGLRO decreased apoptosis and autophagy in both in vivo and in vitro PD models. Further in vitro studies showed that HAGLRO negatively regulated miR-100 expression, and HAGLROS regulated apoptosis and autophagy of MPP+-intoxicated SH-SY5Y cells through sponging miR-100. Moreover, ATG10 was identified as a target of miR-100. Besides, suppression of HAGLROS alleviated MPP+-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway. Our findings reveal that upregulation of HAGLROS may contribute to the development of PD via inhibiting apoptosis and autophagy, which may be achieved by regulating miR-100/ATG10 axis and PI3K/AKT/mTOR pathway activation.

Fluoxetine-mediated inhibition of endoplasmic reticulum stress is involved in the neuroprotective effects of Parkinson's disease.

BACKGROUND: Accumulating evidence suggests that Fluoxetine (FLX), an anti-depressant drug, has broad neurobiological functions and neuroprotective effects in central nervous system injury, but its roles in Parkinson's disease (PD) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates rotenone-induced neurodegeneration in PD. METHODS: Male Sprague-Dawley rats were randomly allocated to control, rotenone-treated, rotenone + FLX-treated and FLX-treated groups. Behavioral tests including open field behavioral test and catalepsy measurement were taken to evaluate neurological behavioral measurements. Apoptosis was detected by TUNEL assay. Endoplasmic reticulum (ER)-related gene expressions were detected by qRT-PCR and western blot. Immunohistochemistry was performed to assess dopaminergic neuronal degeneration. RESULTS: We demonstrated that pretreatment with FLX (10.0 mg/kg, i.p.) significantly ameliorated the catalepsy symptom and increased locomotor activity. In addition, FLX markedly reversed the loss of dopaminergic neurons and suppressed the X­box­binding protein 1 (XBP1)/caspase-3-activated ER stress. Furthermore, FLX inhibited rotenone-mediated neurodegeneration through caspase-3-mediated neuronal apoptosis. CONCLUSION: Taken together, our findings indicate that FLX has beneficial neuroprotective effects in PD and FLX might be a potential therapeutic agent for the treatment of PD. In light of its favorable properties, FLX should be evaluated in the treatment of PD as well as related neurologic disorders.

Let-7a inhibits migration of melanoma cells via down-regulation of HMGA2 expression.

This study aimed to investigate the effects of exosomes derived from BM-MSCs transduced with let-7a on B16f10 cells and BM-MSCs. BM-MSCs were transduced with let-7a and the exosomes of them were isolated for further culture of B16f10 cells and BM-MSCs. The migration of B16f10 cells were detected by transwell, proliferation of B16f10 cells and BM-MSCs was examined by MTT method, HMGA2 expression was measured by western blot. In addition, the let-7a secreted level in exosomes and IGF level were measured by RT-PCR and ELISA respectively. Our results showed that the level of let-7a in exosomes derived from Let-7a-transducted BM-MSCs was increased after treated by exosomes. HMGA2 in B16f10 cells was down-regulated and cell survival rate of BM-MSCs was decreased. However, neither cell survival rate of B16f10 cells nor IGF-1 secreted by B16f10 cells in different groups had significant differences. In conclusion, Let-7a contained in exosomes can inhibit the migration of Melanoma cells and inhibit the proliferation of BM-MSCs.

Glutathione-S-Transferase Deletions and Non-arteritic Anterior Ischemic Optic Neuropathy.

In this study, we aimed at investigating the association between glutathione-S-transferase (GSTM1 and GSTT1) deletion genotypes and susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION). We hope our findings may contribute to the understanding NAION pathogenesis and provide some clues for the prevention and treatment of optic diseases. The NAION group contains 113 subjects (33 males and 80 females, mean age 55.3 ± 9.8). And 98 subjects were enrolled in the control group (32 males and 66 females, mean age 56.7 ± 10.2). The individuals involved in the study were matched by gender and age to obtain two homogenous groups. GSTM1- and GSTT1- genotype and the combined genotype were investigated. The genotype distributions in NAION patients were compared with those in the controls. Significantly altered intraocular pressure (IOP) and cup-to-disc ratio (CDR) was detected between NAION patients and controls. An increased risk of NAION was observed among individuals with GSTM1- (P < 0.001). No significant difference was confirmed for GSTT1- (P = 0.290). Individuals with GSTM1-/GSTT1- have a higher susceptibility to NAION (P < 0.001); the GSTM1-/GSTT1+ genotype also had a significantly higher frequency in patients than in controls (P = 0.004). But the genotype of GSTM1+/GSTT1- seems to have no connection with NAION (P = 0.476). In conclusion, in this study, we confirmed the connection between NAION and GSTM1- genotype. But no significant association was observed between GSTT1- genotype and NAION susceptibility. In further analysis regarding combined genotype, a trend of protective effect was detected for GSTT1+ genotype. It is indicated by our result that oxidative compounds might play an important part in the pathogenesis of NAION.

Serum and Vitreous Concentrations of Omentin-1 in Diabetic Retinopathy.

OBJECTIVE: Omentin, a new discovered adipokine, is implicated to inhibit inflammation. Inflammation is one important mechanism of diabetic retinopathy (DR). The purpose of this work was to evaluate serum and vitreous concentrations of omentin-1 in patients with diabetic retinopathy (DR). METHODS: This study enrolled 204 diabetic patients (60 without DR, 49 with NPDR, and 95 with PDR) and 65 control subjects. RESULTS: Serum and vitreous omentin-1 levels in PDR patients were markedly decreased compared with those in the other three groups. NPDR patients showed reduced vitreous omentin-1 compared with patients without DR. In addition, control subjects had significantly higher levels of serum and vitreous omentin-1 compared with diabetic patients without DR, NPDR patients, and PDR patients. In addition, serum/vitreous omentin-1 ratio was positively correlated with the development and severity of DR. CONCLUSION: Serum and vitreous omentin-1 levels, as well as serum/vitreous omentin-1 ratio, are correlated with the presence and severity of DR.

A novel PAX6 deletion in a Chinese family with congenital aniridia.

Aniridia is a rare, congenital ocular disorder with the characteristics of incomplete formation of the iris caused by the mutations of the paired box gene-6 (PAX6). To investigate the clinical characterization and the underlying genetic defect in a Chinese family with autosomal dominant aniridia, we recruited the family members who underwent comprehensive ophthalmic examination. A novel heterozygous PAX6 deletion mutation c.796 del G (p.A266 fs) (GenBank ID: KP255960) in exon 10 was exclusively observed in all affected individuals but not in any of the unaffected family members or unrelated controls. The PAX6 mRNA level was about 50% lower in patients with aniridia than in unaffected family members, indicating that this mutation caused nonsense-mediated mRNA decay. In conclusion, we identified a novel deletion mutation in the PAX6 gene resulting in an abnormal PAX6 COOH-terminal extension in the Chinese family with aniridia. Our study further expands the mutation spectrum of PAX6.

Detection of Delta-like 1 ligand for the diagnosis of tuberculous meningitis: An effective and rapid diagnostic method.

OBJECTIVE: To investigate the diagnostic value of Delta-like 1 ligand (DLL1) in cerebrospinal fluid (CSF) and serum, in tuberculous meningitis (TBM). METHODS: Patients with a definite diagnosis of central nervous system infection (TBM, viral meningitis/encephalitis or bacterial meningitis) were prospectively enrolled alongside patients with intracranial metastatic tumour and patients with no diagnosis (who served as controls). DLL1 content in CSF and serum was measured quantitatively by enzyme-linked immunosorbent assay; analyses were blinded. RESULTS: A total of 173 patients were enrolled: 62 with TBM; 38 with viral meningitis/encephalitis; 26 with bacterial meningitis; 17 with intracranial metastatic tumour; 30 with no diagnosis. CSF DLL1 content was highest for TBM; there were no differences in CSF DLL1 between the other groups. Serum DLL1 content was highest for the TBM and intracranial metastatic tumour groups, with significant differences between the TBM group and the viral meningitis/encephalitis, bacterial meningitis and nondiagnosed groups. There were no differences in serum DLL1 between the viral meningitis/encephalitis, bacterial meningitis and nondiagnosed groups, or between the TBM group and the tumour group. CONCLUSION: As a new biomarker, DLL1 may be of great clinical importance in the diagnosis of TBM.