ACT001 Relieves NMOSD Symptoms by Reducing Astrocyte Damage with an Autoimmune Antibody.

Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system inflammatory demyelinating disease, the pathogenesis of which involves autoantibodies targeting the extracellular epitopes of aquaporin-4 on astrocytes. We neutralized the AQP4-IgG from NMOSD patient sera using synthesized AQP4 extracellular epitope peptides and found that the severe cytotoxicity produced by aquaporin-4 immunoglobin (AQP4-IgG) could be blocked by AQP4 extracellular mimotope peptides of Loop A and Loop C in astrocyte protection and animal models. ACT001, a natural compound derivative, has shown anti-tumor activity in various cancers. In our study, the central nervous system anti-inflammatory effect of ACT001 was investigated. The results demonstrated the superior astrocyte protection activity of ACT001 at 10 µM. Furthermore, ACT001 decreases the behavioral score in the mouse NMOSD model, which was not inferior to Methylprednisolone Sodium Succinate, the first-line therapy of NMOSD in clinical practice. In summary, our study showed that astrocytes are protected by specific peptides, or small molecular drugs, which is a new strategy for the treatment of NMOSD. It is possible for ACT001 to be a promising therapy for NMOSD.

Differential patterns of interhemispheric functional connectivity between AQP4-optic neuritis and MOG-optic neuritis: a resting-state functional MRI study.

BACKGROUND: Several neuroimaging studies demonstrated that optic neuritis (ON) leads to functional and anatomical architecture changes in the brain. The alterations of interhemispheric functional connectivity (IFC) in patients with AQP4-ON and myelin oligodendrocyte glycoprotein (MOG)-ON are not well understood. PURPOSE: To investigate the differential patterns of VMHC in patients with AQP4-ON and MOG-ON. MATERIAL AND METHODS: Twenty-one patients with AQP4-ON, 11 patients with MOG-ON, and 34 healthy controls underwent resting-state MRI scans. One-way ANOVA was used to identify regions in which the zVMHC differed among the three groups. Post hoc two-sample t-tests were then conducted to compare zVMHC values between pairs of groups. Pearson correlation analysis was conducted to reveal relationships between mean zVMHC values and clinical variables in the AQP4-ON and MOG-ON groups. RESULTS: The results revealed significant differences in zVMHC values in the PreCG among the three groups. Compared to the control group: the AQP4-ON group showed significantly lower VMHC values in the superior temporal gyrus, inferior frontal gyrus, and PreCG; and the MOG-ON group showed significantly higher zVMHC values in the PostCG. Compared to the AQP4-ON group, the MOG-ON group showed significantly lower zVMHC values in the PreCG/PostCG (voxel-level P<0.01, GRF correction, cluster-level P<0.05). CONCLUSION: Patients with AQP4-ON and those with MOG-ON showed abnormal VMHC in the motor cortices, sensorimotor cortices, and frontal lobe, possibly indicating impaired sensorimotor function in patients with ON. Moreover, differential patterns of VMHC in patients with AQP4-ON, compared to patients with MOG-ON, might serve as a clinical indicator for classification of ON.

Etiology, localization of the lesion, and prognosis for patients firstly diagnosed in ophthalmology department with oculomotor nerve palsy. / é¦–è¯ŠäºŽçœ¼ç§‘çš„åŠ¨çœ¼ç¥žç»éº»ç—¹æ‚£è€ ç— å› ã€ç— å˜å®šä½åŠé¢„åŽ.

OBJECTIVES: Oculomotor nerve palsy is a kind of disease with many causes, showing eye movement disorders, abnormal eyelid position, and/or damage of the pupil. The etiology of oculomotor nerve palsy in different departments is different. The study discussed the etiology, localization of the lesion, and prognosis for oculomotor nerve palsy firstly diagnosed in department of ophthalmology. METHODS: Clinical data of 137 hospitalized patients with oculomotor nerve palsy at the Department of Ophthalmology, the First Medical Center of PLA General Hospital from 2009 to 2018 were retrospectively collected. The etiology and its distribution characteristics in different age groups, the location of the lesion, and the prognosis of patients were analyzed. RESULTS: In 137 patients, the top 3 causes for oculomotor nerve palsy were head trauma (38.69%), cavernous sinus lesions (12.40%), and orbital inflammation (9.49%). Other causes included intracranial aneurysm, the intracranial space-occupying lesion, cerebral vessel diseases, infection, orbital tumors, diabetes, the operation of nasal cavity. Traumatic oculomotor nerve palsy was more common in young adults aged 20-49 years and in the patients with cerebral vascular disease in elderly people aged 60-69 years, while diabetic oculomotor nerve palsy is common in middle-aged and elderly people aged 50-69 years. The age distribution of other etiological types was relatively balanced. Seventy-five cases of orbital apex lesions were due to trauma, inflammation, infection, and tumor; 40 cases of cavernous sinus lesions were due to inflammation, tumor, and thrombosis; 6 cases of subarachnoid lesions were due to aneurysms, tumors, and trauma; 5 cases were oculomotor nucleus lesions were due to infarction; 11 cases could not be allocated because of unknown etiology. After treatment, the corrected visual acuity of oculomotor nerve palsy side was not significantly improved. The patients with oculomotor nerve palsy caused by intracranial aneurysm, cerebrovascular disease, and diabetes mellitus had the highest proportion of partial or complete recovery from ptosis and ocular dyskinesia. CONCLUSIONS: Oculomotor nerve palsy is a common cause of ophthalmoplegia and diplopia. Head trauma, cavernous sinus lesions, and orbital inflammation are the most common causes for oculomotor nerve palsy first diagnosed in ophthalmology department. Traumatic oculomotor nerve palsy is common in adolescents. Oculomotor nerve palsy caused by diabetes and cerebrovascular disease are common in the middle-aged and elderly people. Most of the lesions locate in the orbital apex and cavernous sinus. The prognosis of corrected visual acuity is poor. The prognosis of ptosis and ocular dyskinesia caused by intracranial aneurysm, cerebrovascular disease, and diabetes is good. Figuring out the cause timely and accurately is the basis and key to treat oculomotor nerve palsy.

Radiomics Analysis of DTI Data to Assess Vision Outcome After Intravenous Methylprednisolone Therapy in Neuromyelitis Optic Neuritis.

BACKGROUND: Neuromyelitis optica-optic neuritis (NMO-ON) patients are routinely treated with intravenous methylprednisolone (IVMP). For the patients nonresponsive to IVMP, more effective but aggressive therapy of plasma exchange (PE) should be employed instead of IVMP in the first line. PURPOSE: To assess the visual outcomes of NMO-ON patients after IVMP by radiomics analysis of whole brain diffusion tensor imaging (DTI) data. STUDY TYPE: Retrospective. POPULATION: In all, 57 NMO-ON patients receiving IVMP therapy for 3 days. FIELD STRENGTH/SEQUENCE: 3.0T; DTI images acquired by a single-shot echo planar image sequence; T1 images acquired by 3D fast spoiled gradient echo (3D-FSPGR) MRI. ASSESSMENT: In all, 200 DTI measures were extracted from the DTI data and employed as features to construct a radiomics assessment model for visual outcomes of NMO-ON patients after IVMP. The assessment performance was evaluated by area under the receiver operating characteristic curve (AUC), classification accuracy (ACC), sensitivity, specificity, and positive and negative predicted values (PPV and NPV). The selected DTI measures would reveal the white matter impairments related to visual recovery of NMO-ON patients. STATISTICAL TESTS: The relationship between the selected DTI measures and the clinical visual characteristics were investigated by Pearson correlation, Spearman's rank correlation, and one-way analysis of variance analysis. RESULTS: The radiomics model obtained an ACC of 73.68% (P = 0.002), AUC of 0.7931, sensitivity of 0.6207, specificity of 0.8571, PPV of 0.8182, and NPV of 0.6857 in assessing visual outcomes of the NMO-ON patients after IVMP treatment. The selected DTI measures revealed white matter impairments related to the visual outcomes in the white matter tracts of vision-relevant regions, motor-related regions, and corpus callosum. The white matter impairments were found significantly correlated with the disease duration and the length of lesions in the optic nerve. DATA CONCLUSION: Radiomics analysis of DTI data has great potential in assessing visual outcomes of NMO-ON patients after IVMP therapy. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:1365-1373.

MRI Histogram Texture Feature Analysis of the Optic Nerve in the Patients with Optic Neuritis.

Objective To evaluate the optic nerve impairment using MRI histogram texture analysis in the patients with optic neuritis.Methods The study included 60 patients with optic neuritis and 20 normal controls. The coronal T2 weighted imaging (T2WI) with fat saturation and enhanced T1 weighted imaging (T1WI) were performed to evaluate the optic nerve. MRI histogram texture features of the involved optic nerve were measured on the corresponding coronal T2WI images. The normal optic nerve (NON) was measured in the posterior 1/3 parts of the optic nerve. Kruskal-Wallis one-way ANOVA was used to compare the difference of texture features and receiver operating characteristic (ROC) curve were performed to evaluate the diagnostic value of texture features for the optic nerve impairment among the affected optic nerve with enhancement (ONwEN), affected optic nerve without enhancement (ONwoEN), contralateral normal appearing optic nerve (NAON) and NON.Results The histogram texture Energy and Entropy presented significant differences for ONwEN vs. ONwoEN (both P=0.000), ONwEN vs. NON (both P=0.000) and NAON vs. NON (both P<0.05). ROC analysis demonstrated that the area under the curve (AUC) of histogram texture Energy were 0.758, 0.795 and 0.701 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON, AUC of Entropy were 0.758, 0.795 and 0.707 for ONwEN vs. ONwoEN, ONwEN vs. NON and NAON vs. NON.Conclusions The altered MRI histogram texture Energy and Entropy could be considered as a surrogate for MRI enhancement to evaluate the involved optic nerve and normal-appearing optic nerve in optic neuritis.

Comparison of field-of-view optimized and constrained undistorted single-shot diffusion-weighted imaging and conventional diffusion-weighted imaging of optic nerve and chiasma at 3T.

PURPOSE: Single-shot echo-planar imaging is the conventional diffusion-weighted imaging (C-DWI) sequence for evaluating orbital disease. However, its utility is restricted in small organs like the chiasma and optic nerve. This study was conducted to investigate the utility of field-of-view optimized and constrained undistorted single-shot diffusion-weighted imaging (FOCUS-DWI) for evaluating the chiasma and optic nerve in acute optic neuritis, making comparisons with C-DWI. METHODS: FOCUS-DWI and C-DWI were performed on 36 acute optic neuritis patients and 16 normal controls. Two readers assessed image quality using 5-point Likert scales. Differences in the visual assessments and apparent diffusion coefficient (ADC) values between C-DWI and FOCUS-DWI were evaluated. Inter-observer agreement in the qualitative data was assessed using Cohen's kappa coefficients. Inter- and intra-observer agreements in the ADC values were evaluated using intraclass correlation coefficients. RESULTS: FOCUS-DWI was superior to C-DWI in all aspects of the image evaluations. The Cohen's kappa coefficients for FOCUS-DWI were almost perfect (0.81-1) or substantial (0.61-0.80) for all the image quality categories. In the FOCUS-DWI images, the structural conspicuity of the chiasma and canalicular and cisternal segments was significantly superior on coronal views than on axial views (P < 0.0001). ROC analysis showed that in optic neuritis patients, the diagnostic value of ADC measurements on FOCUS-DWI was higher than ADC values measured on C-DWI. CONCLUSION: The FOCUS-DWI technique can provide substantial improvements over C-DWI for imaging different aspects of the optic nerve and chiasma. The coronal scan direction is more suitable than the axial scan direction for FOCUS-DWI.

Altered Retinal Nerve Fiber Layer Thickness and Choroid Thickness in Patients with Migraine.

BACKGROUND: Migraine is a chronic neurological disorder. However, its pathogenesis is still unclear. This study aimed to measure the posterior ocular structure in patients with migraine using enhanced depth imaging (EDI)-optical coherence tomography (OCT) and explore the probable pathogenesis of migraine. METHODS: A total of 115 patients diagnosed with migraine and 50 healthy volunteers were recruited. These participants underwent an ocular examination to exclude the ocular diseases. Retinal nerve fiber layer thickness, macular thickness, and choroid thickness were assessed using EDI-OCT. RESULTS: The nasal peripapillary retinal nerve fiber layer (pRNFL) was significantly thinner in the migraine with aura group (p = 0.001) than that in the control group. The inferior inner macular layer was thinner in the migraine with aura group (p = 0.005). The 3 subfields of choroid were significantly thinner in the migraine with aura group (p = 0.044, 0.008, and 0.029). However, there was no difference between the migraine without aura group and the control group. The nasal pRNFL in migraine with aura was negatively correlated with the product of duration (months) and number of attacks/month (p = 0.039). CONCLUSION: The changes in the ocular posterior structure may serve as evidence of the trigeminovascular system mechanism underlying migraine and transneuronal retrograde degeneration of the primary visual cortex, which reflects the cortical spreading depression.

An Improved Fast Self-Calibration Method for Hybrid Inertial Navigation System under Stationary Condition.

The navigation accuracy of the inertial navigation system (INS) can be greatly improved when the inertial measurement unit (IMU) is effectively calibrated and compensated, such as gyro drifts and accelerometer biases. To reduce the requirement for turntable precision in the classical calibration method, a continuous dynamic self-calibration method based on a three-axis rotating frame for the hybrid inertial navigation system is presented. First, by selecting a suitable IMU frame, the error models of accelerometers and gyros are established. Then, by taking the navigation errors during rolling as the observations, the overall twenty-one error parameters of hybrid inertial navigation system (HINS) are identified based on the calculation of the intermediate parameter. The actual experiment verifies that the method can identify all error parameters of HINS and this method has equivalent accuracy to the classical calibration on a high-precision turntable. In addition, this method is rapid, simple and feasible.

Detection of Thyroid Abnormalities in Aquaporin-4 Antibody-Seropositive Optic Neuritis Patients.

OBJECTIVE: This study retrospectively analyzed the frequency of anti-thyroid antibodies (ATAs) and thyroid disease in patients with optic neuritis (ON). METHODS: Tests of serum thyroglobulin (TG) and thyroid peroxidase (TPO) antibodies and thyroid function were performed in 97 ON patients. Blood also was drawn to test for AQP4-Ab using cell-based and enzyme-linked immunosorbent assays. Comparisons of the frequencies of ATAs, thyroid diseases and thyroid function were performed based on AQP4-Ab status. RESULTS: Seropositive AQP4-Ab was found in 47/97 (48.5%) patients. ATA was considered positive in 34/97 (35.1%) patients. The prevalence of ATA was two times higher (P = 0.019) in the AQP4-Ab+ group compared to the AQP4-Ab- group. AQP4-Ab+ ON patients exhibited lower FT3 (P = 0.006) and FT4 (P = 0.025) levels and a higher prevalence of definite Hashimoto thyroiditis (HT) (P = 0.005). Among AQP4-Ab+ patients, those with HT had a worse visual outcome than non-HT patients. CONCLUSION: A high prevalence of ATAs and HT was found in AQP4-Ab+ ON patients, and AQP4-Ab+ patients with HT exhibited worse visual outcomes than non-HT patients.

Heme oxygenase-1 (HO-1) protects human lens epithelial cells (SRA01/04) against hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis.

OBJECTIVES: This study aimed to investigate the protective role of heme oxygenase-1 (HO-1) in H2O2-induced oxidative stress and apoptosis in human lens epithelial cells (hLEC; SRA01/04). METHODS: SRA01/04 cells were exposed to a hydrogen peroxide (H2O2) concentration gradient and inducers of HO-1 such as cobalt protoporphyrin (CoPP) and zinc protoporphyrin (ZnPP), respectively. In addition, an RNA silencing experiment was conducted to investigate the HO-1 function in this study. A Cell Counting Kit-8 (CCK-8) assay was used to measure cell viability. Western blot and ELISA were used to detect the level of HO-1 expression. In our study, hLECs were exposed to 400 µM hydrogen peroxide (H2O2) for 24 h with or without pretreatment with 10µΜ CoPP or 10µΜ ZnPP, respectively. Double immunofluorescence staining was used for cell identification and the qualitative expression of HO-1. Expression of HO-1 was monitored using Western blot and ELISA. Intracellular reactive oxygen species (ROS) were detected by flow cytometry analyses; commercial enzymatic kits were used to measure the levels of glutathione (GSH), as well as superoxide dismutase (SOD). The proportion of cell apoptosis was quantified by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. The expression of caspase family (-8, -3) proteins was measured by Western blot analysis. RESULTS: HO-1 significantly restored the cell viability under H2O2 injury via reducing the generation of ROS and increasing the levels of SOD and GSH activity. Moreover, HO-1 also inhibited H2O2-induced caspase-8 and caspase-3 proteins, thus significantly reducing the apoptosis of SRA01/04. An RNA silencing experiment demonstrated the increased resistance of LECs to oxidative stress specifically for increased levels of HO-1. CONCLUSIONS: These findings suggested that HO-1 protects human lens epithelial cells from H2O2-induced oxidant stress by upregulating antioxidant enzyme activity, reducing ROS generation, and thus inhibiting caspase family-dependent apoptosis.

Interocular symmetry of the peripapillary choroidal thickness and retinal nerve fibre layer thickness in healthy adults with isometropia.

BACKGROUND: The aim of this study was to determine the interocular differences in the peripapillary retinal nerve fibre layer (RNFL), peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) in healthy adults with isometropia, using enhanced depth imaging optical coherence tomography (EDI SD-OCT). METHODS: One hundred healthy Chinese adults with spherical equivalents of ≤ ±3 dioptres and interocular differences of <0.5 dioptres were prospectively enrolled in this study. They underwent RNFL and PCT measurements via EDI SD-OCT, with a 3.4 mm scan circle centred on the optic nerve head. Subfoveal choroidal thickness (SFCT) measurements were also taken with a horizontal line scan centred on the macula. Right and left eyes were compared by a paired t-test, and the interocular differences were calculated. The agreement and correlations of the RNFLs, PCTs and SFCTs between the right and left eyes were analysed. RESULTS: Eighty-six subjects (172 eyes) were included in the final analysis, consisting of 44 (51.6 %) males and 42 (48.8 %) females; 55 (63.9 %) had emmetropia and 33 (36.1 %) had ametropia. The RNFL was statistically significantly thicker in the right eyes when compared to the left eyes in the temporal quadrant, and thinner on average in the nasal superior quadrant (p < 0.05). However, the differences in the choroidal thicknesses in all of the quadrants between the right and left eyes were not statistically significant. The tolerance limits of the average RNFL were -21.1 µm and 7.1 µm, and the mean and standard deviation of the interocular difference in the average PCT was -2.2 ± 24.2 µm. The RNFLs and PCTs in all of the locations in the right eyes were significantly correlated with those in the left eyes. However, no significant associations between the age, sex, interocular asymmetry of spherical the equivalent or interocular differences in the RNFL and PCT were detected. CONCLUSION: The PCT did not differ significantly between the right and left eyes, although interocular asymmetry of the RNFL existed in this Chinese population with isometropia.

Research Advances in Biomarkers for Demyelinating Optic Neuritis.

Optic neuritis refers to all inflammatory diseases in the optic nerve. The most common type is demyelinating optic neuritis. Biomarkers can indicate its pathophysiological process and thus are useful in disease diagnosis and treatment. This article reviews the known biomarkers for demyelinating optic neuritis.

Early spatiotemporal characterization of microglial activation in the retinas of rats with streptozotocin-induced diabetes.

BACKGROUND: Microglial activation has been recognized as a neuropathological feature in diabetic retinopathy. But the early spatiotemporal characterization of microglial activation in the retina and the optic nerve of diabetic animals has not been fully investigated. The purpose of this study was to investigate early sequential changes of microglia in the retinas of rats with streptozotocin-induced diabetes. Microglia in the optic nerves of rats with streptozotocin-induced diabetes were also studied. METHODS: In 4-week, 8-week, and 12-week diabetic and normal control rats, microglial activation in the retinas and optic nerves was evaluated by immunolabeling with OX-42 antibody. Density, proportion of activation, and laminar distribution of retinal microglia were quantified. The retinal mRNA level of Iba-1, a microglial-specific marker, was measured by real-time PCR. RESULTS: The density of retinal microglia was not different between diabetic and control rats, but the proportion of activated microglia increased significantly in diabetic rats at each time point. The proportion of microglia increased obviously in the nerve fiber layer and the ganglion cell layer while decreasing in the inner plexiform layer in 12-week diabetic rats. Moreover, retinal Iba-1 mRNA expression increased in 8-week and 12-week diabetic rats. Processes of microglia in the optic nerves of control rats were aligned with the long axis of nerve fibers, while the alignment was disturbed in diabetic rats. CONCLUSIONS: Morphology, proportion of activation, distribution, and mRNA expression of retinal microglia changed characteristically with the progression of the disease in early-stage diabetic rats.

Intraoperative high-field magnetic resonance imaging combined with functional neuronavigation in resection of low-grade temporal lobe tumors.

BACKGROUND: The aim of this study is to investigate the role of intraoperative MR imaging in temporal lobe low-grade glioma (LGG) surgery and to report the surgical outcome in our series with regard to seizures, neurological defects, and quality of life. METHODS: Patients with temporal lobe contrast-nonenhancing gliomas who presented with seizures in the course of their disease were enrolled in our prospective study. We non-randomly assigned patients to undergo intraoperative magnetic resonance imaging (iMRI)-guided surgery or conventional surgery. Extent of resection (EOR) and surgical outcomes were compared between the two groups. RESULTS: Forty-one patients were allocated in the iMRI group, and 14 were in the conventional group. Comparable EOR was achieved for the two groups (p = 0.634) although preoperative tumor volumes were significantly larger for the iMRI group. Seizure outcome tended to be better for the iMRI group (Engel class I achieved for 89.7% (35/39) vs 75% (9/12)) although this difference was not statistically different. Newly developed neurological deficits were observed in four patients (10.3%) and two patients (16.7%), respectively (p = 0.928). Free of seizures and neurological morbidity led to a return-to-work or return-to-school rate of 84.6% (33/39) vs 75% (9/12), respectively (p = 0.741). CONCLUSIONS: Our study provided evidence that iMRI was a safe and useful tool in temporal lobe LGG surgery. Optimal extent of resection contributed to favorable seizure outcome in our series with low morbidity rate, which led to a high return-to-work rate.

[Raise awareness of IgG4 relative ocular disease].

Purpose IgG4-related ocular disease is a chronic systemic disease with lymphocyte abnormal. The lacrimal glands, extraocular muscles and infraorbital nerve were often involved which was often the first symptom of systemic disease. While ophthalmologists did not know this disease well. They usually misdiagnosed it as idiopathic inflammatory pseudotumor, thyroid-associated ophthalmopathy etc, which resulted in delayed treatments. Here pathogenesis, clinical features and treatment methods of IgG4-relative ocular disease were described in order to improve awareness of this ocular disease, reduce clinical misdiagnosis, improve disease prognosis and standardized treatment. As the incidence of this disease increased in recent years, it is very necessary to improve awareness of the disease for ophthalmologists.

[Relationship between the levels and variation of CXCL12, PDGF, CXCL14 in cerebrospinal fluid of optic neuritis and neuromyelitis optica].

OBJECTIVE: To explore the predictive value of the prognosis and outcome for optic neuritis (ON) and neuromyelitis optica (NMO) by investigating the levels and variation of CXCL12, PDGF and CXCL14 in CSF of patients with ON and NMO. METHODS: Retrospective study. Thirty-five patients with ON, 10 patients with NMO and 10 patients with cerebral venous sinus thrombosis (CVST) were scheduled in the research unit from September 2012 to September 2013 in Neuro-Ophthalmology Department of PLA General Hospital. Clinical data and cerebrospinal fluid (CSF) parameters were collected. CXCL12, PDGF and CXCL14 concentrations were measured in CSF using enzyme linked immunosorbent assay (ELISA). The CXCL12, PDGF and CXCL14 levels in CSF were compared by using ANOVA in different diseases with different phases and recurrent cases found by MRI. Multiple comparisons were used by LSD method. The comparison of positive rate for MRI in ON different phases was used by exact probability. Meanwhile, correlation analysis was conducted between CXCL12, PDGF, CXCL14 and white blood cells (WBC), IgG and protein in CSF. RESULTS: Compared with NMO group (3.69±0.35, 2.04±0.24, 7.05±0.94), the CXCL12, PDGF and CXCL14 levels in CSF were higher in ON (4.39±0.51, 2.51±0.39, 8.65±1.55) and CVST(4.84± 0.49, 2.79±0.47, 10.53±1.11) group (F=14.593, 10.060, 10.003,P<0.001, <0.001, <0.001), especially the CXCL12, PDGF and CXCL14 levels in CSF of CVST group patients were higher than that in ON group. Among them, the CXCL12 and PDGF levels in CSF were higher in acute phase of ON (4.63±0.50, 2.65±0.40) and CVST(4.84±0.49, 2.79±0.47) group than stationary phase of ON (4.13±0.39, 2.34±0.32) group (F=8.823, 4.906, P=0.001, 0.012). In addition, 28 of 35 ON patients were conducted the cerebral or orbital magnetic resonance imaging (MRI). The result showed that the CXCL12 and PDGF levels in CSF of patients with positive finding in MRI (3.96±0.30, 2.23±0.16) were higher than those patients with negative finding in MRI (4.64±0.42, 2.62±0.42) (t=-4.754, -2.977, all P<0.01). Besides that, there was higher correlation between the CXCL12 level and PDGF in CSF (P<0.01). CONCLUSIONS: Reduced concentration of cytokine that promoted remyelination such as CXCL12 and PDGF in cerebrospinal fluid of the ON and NMO patients may predict a bad myelin regeneration.

[Research progresses of monoclonal antibodies therapy in neuromyelitis optica].

Neuromyelitis optica (NMO) is a kind of demyelinating disorder that preferentially affects the optic nerves and spinal cord and results in permanent vision loss. There is no effective treatment so far. In recent years, monoclonal antibodies (mAbs) have been applied in a number of clinical drug trials and basic researches in NMO therapy due to its specificity and uniformity. Phase I clinical study found that, symptoms significantly improved in some patients after mAbs treatment. This review will expound the therapy classification, mechanism of action and clinical results involving mAbs, and provide reference for the clinical treatments of NMO.

The involvement of high mobility group 1 cytokine and phospholipases A2 in diabetic retinopathy.

BACKGROUND: Diabetic retinopathy, the main microvascular complications of diabetes and one of the leading causes of blindness worldwide. Interesting reports on the role of inflammatory/proangiogenic high mobility group 1 (HMGB-1) cytokine and phospholipases A2 (PLA2) in neovascularization have diverted our concentration to reveal whether HMGB-1 and PLA2 plays role in diabetic retinopathy. METHODS: We performed our study in streptozotocin (STZ)-induced diabetic rat model. The expression levels of the cytokines, chemokines, and cell adhesion molecules in retinal tissues were evaluated by quantitative RT-PCR. HMGB-1 and PLA2 protein levels along with VEGF, TNF-α, IL-1ß and ICAM-1 levels were also measured. RESULTS: We observed the retinal pericytes, endothelial injury/death and breakdown of blood-retinal barrier (BRB). The protein expression of HMGB-1, PLA2 and IL-1ß were significantly increased in micro vessels from retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM-1 and TNF-α. Further investigation revealed that pericyte death is mediated by HMGB-1-induced cytotoxic activity of glial cells, while HMGB-1 can directly mediate endothelial cell death. Similarly, increased expression of PLA2 represents the diabetic mediated alteration of BRB, perhaps up regulating the VEGF. CONCLUSIONS: Our data suggest that HMGB-1 and PLA2 involved in retinal pericyte and endothelial injury and cell death in diabetic retinopathy. From this study, we suggest that HMGB-1 and PLA2 may be interesting targets in managing diabetic retinopathy.

Characterization of macular thickness changes in Leber's hereditary optic neuropathy by optical coherence tomography.

BACKGROUND: To characterize macular thickness (MT) changes in Leber's hereditary optic neuropathy (LHON) patients by cirrus HD-optical coherence tomography (OCT), and to study the correlation between MT and best corrected visual acuity (BCVA). METHODS: Fifty-two eyes from 52 consecutive LHON patients and 14 eyes from 14 age- and sex-matched healthy controls were scanned by OCT. Affected eyes were classified into five groups according to disease duration (1st group: ≤3 months; 2nd group: 3-6 months; 3rd group: 6-9 months; 4th group: 9-12 months; and 5th group: >12 months). MT was compared and analyzed. The correlation between BCVA and MT was calculated. RESULTS: Less than six months after LHON onset, the cube average thickness (CAT) and the MT in the superior, nasal, inferior, and temporal quadrants of the inner ring and the MT in the nasal quadrant of the outer ring were decreased (P < 0.005); at 3-6 months onset, the MT of the temporal quadrants of the outer ring was decreased (P = 0.045); after 6 months, the MT was significantly thinner in all measurements (P < 0.01) except for the central ring. The BCVA was significantly different between each group and controls (P < 0.05), but there was no significant correlation among the five groups (P = 0.666). There was no significant correlation between the BCVA and CAT (P = 0.893). CONCLUSIONS: The MT thinned before the retinal nerve fiber layer and this occurred with a particular sequence. Our results provide potential diagnostic information for LHON.

[Work hard to develop neuro-ophthalmology in China].

Neuro-ophthalmology is a crossing discipline. Optic neuritis and ischemic optic neuropathy are the hot points of this field. Currently, studies of optic neuritis epidemiology, etiology and clinical features have already been done in china. And the expert consensus of optic neuritis therapy was published. The pathogenesis and treatment of ischemic optic neuropathy is another hot point. We have embarked on the epidemiological study of ischemic optic neuropathy in china. We also appeal the ophthalmologists to pay more attention on the therapy of posterior visual pathway.