ObjectiveTo observe the ocular manifestations and the titer of aquaporin 4 antibody (AQP-4) in NMO patients, and to evaluate the BCVA prognosis in patients with different titers of AQP-4Ab.MethodsA retrospective case study. From September 2009 to March 2014, 132 NMO patients diagnosed in Department of Neurology and Ophthalmology in Huashan Hospital of Fudan University were included in the study. Among the patients, 74 patients (56.06%) were involved in optic nerve for the first time, among which 63 patients (47.72%) were involved in optic nerve alone, and 11 patients (8.33%) were involved in optic nerve and spinal cord at the same time. The recurrence rate was 62.88% (twice or more). All patients underwent BCVA, slit lamp microscope, fundus examination, thyroid function, sex hormones, and serum AQP-4Ab detection. BCVA was recorded at admission and before discharge from hospital, and worse BCVA was recorded in binocular patients. The BCVA of patients with different titers of AQP-4Ab were analyzed comparatively.ResultsAmong the 74 patients with optic nerve involved in the first onset, 50 patients with BCVA＜0.1 at the initial diagnosis (67.57%); AQP-4Ab positive was found in 56 patients, which including 13, 9 and 34 patients of AQP-4Ab titer 5 - 60, 61 - 100 and ＞100 RSRU/ml. After 2 weeks of treatment, BCVA improved in 40 patients (71.42%), including 11 (84.62%), 6 (66.67%) and 23 (67.64%) of AQP-4Ab titer 5 - 60, 61 - 100 and ＞ 100 RSRU/ml. Among 132 patients, 98 patients (74.24%) were AQP-4Ab positive. There were 73 patients (55.30%) with abnormal immune rheumatoid index.ConclusionsThe optic nerve is involved in 56.06% patients with NMO for the first time, and 67.57% of the patients had poor vision with BCVA＜0.1. BCVA prognosis is better in patients with serum AQP-4Ab titer of 5 - 60 RSRU/ml.
ObjectiveTo analyze the clinical features and prognosis of adult optic neuritis patients with positive serum myelin oligodendrocyte glycoprotein antibody (MOG-ON) or aquaporin 4 antibody (AQP4-ON).MethodsA retrospective study. From December 2015 to February 2018, in the Beijing Chaoyang Hospital of Capital Medical University and Chinese PLA General Hospital, 162 eyes of 132 patients with positive serum MOG antibody and AQP4 were included in the study. There were 42 MOG-ON patients (49 eyes, 31.8%), 90 AQP4-ON patients (113 eyes, 68.2%). The clinical features of optic neuritis (annual recurrence frequency, incidence of optic disc edema), brain and optic nerve enhanced MRI, serum autoimmune antibodies and cerebrospinal fluid test results were compared between MOG-ON and AQP4-ON patients. All patients were treated with intravenous methylprednisolone sodium succinate in the acute phase and then switched to oral prednisone acetate tablets. The average follow-up time was 15 months. The glucocorticoid dependence, visual prognosis, spinal cord symptoms, and myelitis at the last follow-up were comparatively analyzed between MOG-ON and AQP4-ON patients. The comparison of the count data was performed by χ2 test, and the measurement data were compared by t test.ResultsCompared with AQP4-ON patients, MOG-ON patients had higher annual recurrence frequency (t=3.760, P=0.005), higher incidence of optic disc edema (χ2=14.777, P＜0.001), higher incidence of hormone dependence (χ2=25.496, P＜0.001), and better visual prognosis (χ2=28.759, P＜0.001). MOG-ON patients were more likely to involve the optic nerve, AQP4-ON patients were more likely to involve the optic chiasm and the optic tract. There was a significant difference in the location of lesions between MOG-ON and AQP4-ON patients (χ2= 5.447, P= 0.015). The proportion of AQP4-ON patients with autoimmune antibodies was significantly higher than that of MOG-ON patients (χ2 = 20.453, P＜0.001). The results of cerebrospinal fluid test showed that the white blood cell count of patients with MOG-ON and AQP4-ON were within the normal range, but the IgG level of AQP4-ON patients was significantly higher than that of MOG-ON patients (t=8.669, P＜0.001). At the last follow-up, there were 7 and 29 patients of myelitis in MOG-ON and AQP4-ON patients respectively (χ2=3.494, P=0.046).ConclusionsThe clinical characteristics of MOG-ON were different from AQP4-ON. The incidence of optic disc edema and recurrence rate were higher, but the proportion of autoimmune antibodies was lower. MOG-ON was more likely to show hormone dependence, but the visual prognosis was better. AQP4-ON was easily involved in optic chiasm and optic tract, and the incidence of myelitis was higher.
ObjectiveTo analyze the clinical features and prognosis factors of aquaporin 4 (AQP4) antibody-positive neuromyelitis optica spectrum disorders related optic neuritis (NMOSD-ON). MethodsAn ambidirectional cohort study. From June 1, 2015 to June 1, 2019, 103 patients with AQP4 antibody-positive NMOSD-ON in Department of Neuro-ophthalmology, The First Medical Center of PLA General Hospital were included. All patients of followed-up period were ≥24 months. According to the best corrected visual acuity (BCVA) at the last follow-up, the affected eyes were divided into the low vision group [log of minimum resolution angle (logMAR) BCVA≥1.0] and the non-low vision group (logMAR BCVA＜1.0), 66 and 37 cases, respectively. The two groups of patients were compared the genernal clinical characteristics, and the logistic regression model and COX proportional hazard model were used to analyze the relevant factors affecting the patient's visual prognosis and recurrence. ResultsAmong the 103 cases, 96 cases (93.2%, 96/103) were female; 94 cases (91.3%, 94/103) had unilateral disease; 48 cases (46.6%, 48/103) were the first onset; 85 cases (82.5%, 85/103) were effected by eye pain or orbital pain; 21 cases (20.4%, 21/103) had optic disc edema; 51 cases (49.5%, 51/103) serologically autoimmune antibody test were positive. Orbital magnetic resonance imaging (MRI) was performed in 101 cases. There was no obvious abnormal signal in visual pathways except for 5 cases (5.0%, 5/101); 96 cases (95.0%, 96/101) had abnormal signal in the visual path, and the optic nerve was found in the orbit; 52 cases had abnormal optic nerve in orbital segment (51.5%, 52/101); 37 cases (35.9%, 37/103) recurred within 24 months. The recovery of logMAR BCVA after the first onset and the logMAR BCVA at the first onset, at 6 months of follow-up in two groups were 1.4±1.0, 0.3±0.4, 1.9±0.7 and 0.4±0.5, 2.1±0.6, 0.3±0.4, respectively; and there were statistically significant differences between the two groups of patients at different times（Z=－4.967,－7.603,－8.027; P＜0.001). Logistic regression multivariate analysis showed that recovery of BCVA≥1.0 logMAR after the first onset [odds ratio (OR)=226.276, P＜0.001] and the number of attacks (OR=8.554, P=0.003) were independent risk factors for low vision. Multivariate analysis of the Cox proportional hazards model showed the higher the MRI score [hazard ratio (HR)=0.588, P=0.007] and plasma exchange (HR=0.124, P=0.049) in the acute phase were protective factors for recurrence. ConclusionsVision loss accompanied by eye pain or orbital pain is the main symptom of onset AQP4 antibody-positive NMOSD-ON, a small number of patients have disc edema, 49.5% patients serologically autoimmune antibody test are positive. Abnormal optic nerve signals can be seen in 95.0% of patients in orbital MRI, and 51.5% patients have abnormalities in the orbital optic nerve. The worse the recovery of BCVA after the first onset and the greater the number of attacks are unfavorable factors affecting the prognosis of vision. High MRI scores and plasma exchange in the acute phase are favorable factors to prevent the recurrence of the disease.
【摘要】 目的 探討腹水引起的腹內高壓對肝硬化小鼠肺組織水通道蛋白1（AQP1）和水通道蛋白5（AQP5）表達的影響。 方法 雄性美國癌癥研究所（Institudo of Cancer Reseach，ICR）小鼠50只，隨機取10只作正常對照組（腹壓0 cm H2O，1 cm H2O=0.098 kPa），其余40只用四氯化碳建立肝硬化小鼠模型，并隨機分為4組:肝硬化（腹壓0 cm H2O）組、肝硬化（腹壓5 cm H2O）組、肝硬化（腹壓10 cm H2O）組、肝硬化（腹壓20 cm H2O）組，通過腹腔注射不同量的白蛋白生理鹽水形成不同的腹壓，并維持腹壓24 h后取肺組織行病理、免疫組織化學、肺濕/干比值及實時熒光定量PCR檢測AQP1和AQP5 mRNA表達量。 結果 與正常對照小鼠相比，肝硬化小鼠肺AQP5、AQP1表達明顯下降（Plt;0.05）；肝硬化小鼠隨著腹內壓的升高，肺濕/干比值升高，AQP5、AQP1表達相應增加（Plt;0.05）。 結論 肝硬化可以影響肺AQP1、AQP5的表達；肝硬化小鼠隨著腹內壓的升高，AQP1、AQP5表達相應增加，并與肺水腫的嚴重程度密切相關。【Abstract】 Objective To investigate the role of intra-abdominal hypertension caused by ascites on the expression of Aquaporin (AQP) 1 and AQP 5 in the lung of cirrhotic mice. Methods We randomly chose 10 from 50 male Institude of Cancer Research (ICR) mice to form the control group [intra-abdominal pressure (IAP)=0 cm H2O, 1 cm H2O=0.098 kPa]. The model of cirrhosis were prepared by subcutaneous injection of carbon tetrachloride for the rest 40 mice which were then randomly divided into 4 groups: cirrhosis (IAP=0 cm H2O) group, cirrhosis (IAP=5 cm H2O) group, cirrhosis (IAP=10 cm H2O) group, and cirrhosis (IAP=20 cm H2O) group. Saline with different volume of albumin was injected into the peritoneum of each mouse in order to form different IAP. After 24 hours, analysis of pathology, immunochemistry and wet/dry ratio was done for the lungs of these mice; and the expression of AQP1 and AQP5 at the protein and mRNA levels were analyzed by IHC and qRT-PCR. Results Compared with the normal mice, the expression of AQP1 and AQP5 in lungs of cirrhotic mice were significantly lower (Plt;0.05). Both the lung wet/dry ratio and the expression of AQP1 and AQP5 raised with the increase of IAP. Conclusion Cirrhosis can affect the expression of AQP1 and AQP5 in lungs. The expression of AQP5 and AQP1 in lungs of cirrhotic mice increases with the increase of IAP, which is also closely correlated with the severity of pulmonary edema.
ObjectiveTo observe the expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) in the inner limiting membrane (ILM) of diabetic retinopathy (DR) with macular edema, and analyze the correlation between VEGF and AQP4 expression. Methods A cross-sectional study. From September 2019 to September 2020, 38 eyes of 38 patients with DR and idiopathic macular hole (iMH) who underwent vitrectomy (PPV) combined with ILM stripping at the Hangzhou campus of The Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. Among them, there were 25 males and 13 females who aged 37-76 years old, average age was 59±10 years old; All eye included 15 right eyes and 23 left eyes. iMH and DR included 9 eyes in 9 cases and 29 eyes in 29 cases, respectively, and they were divided into iMH group and DR group. The DR group was divided into DME group and no DME group according to whether it was accompanied by diabetic macular edema (DME), with 14 eyes and 15 eyes respectively. After the stripped ILM tissue was fixed, immunofluorescence analysis was performed to obtain a picture of the fluorescence mode of AQP4 and VEGF, and the fluorescence intensity value of VEGF and AQP4 was measured by Image J software. The differences of VEGF and AQP4 immunofluorescence values in the specimens between groups were compared by one-way analysis of variance. The correlation between the fluorescence intensity of AQP4 and the fluorescence intensity of VEGF was analyzed by Pearson correlation analysis. Results The average fluorescence intensity values?of VEGF and AQP4 in ILM specimens of DME group, no DME group and iMH group were 38.96±7.53, 28.25±3.12, 30.07±4.84 and 49.07±8.73, 37.96±6.45, 38.08±5.04, respectively. The average fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DME group was significantly higher than that of the no DME group and iMH group, and the difference was statistically significant (F=13.977, 9.454; P＜0.05). The average fluorescence intensity values of VEGF and AQP4 on IML specimens in the DR group were 33.80±7.91, 43.76±9.44, respectively. The results of Pearson correlation analysis showed that the fluorescence intensity of VEGF and AQP4 in the ILM specimens of the DR group was significantly positively correlated (r=0.597, P=0.003). ConclusionsThe expressions of VEGF and AQP4 in ILM of eyes with DR and DME are significantly increased compared with those without DME. The expression of VEGF and AQP4 in ILM of eyes with DR is positively correlated.
Objective
To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD).
Methods
Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed.
Results
Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P＞0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048).
Conclusions
The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis.
ObjectiveTo observe the effects of aquaporin 1 (AQP1) on the proliferation and migration of endothelial progenitor-endothelial progenitor cells (EPC).MethodsBone marrow cells of AQP1 wild-type (WT) (n=6) and knockout-type (KO) mice (n=6) were isolated and differentiated into EPC in vitro. Immunofluorescence was used to detect cell surface antigens to identify EPC. Live cell kinetic imaging and quantification technology, transwell migration assays, as well as scratch test were used to compare the function of EPC between AQP1 WT and KO mice.ResultsEPC culture showed that cells were initially suspended and gradually adhered to typical mesenchymal stem cells within 7 days. After cultured on special medium for endothelial cells they were adhered and differentiated, and fusiform or polygonal, paving stone-like EPC were observed around 14 days. When cultured by special medium of EPC, CD133 and CD31 were positively detected after 7 days, and CD34 and Flk-1 were positively detected after 14 days. Positive expression of AQP1 was only detected in EPC of AQP1 WT mice. Functional studies of EPC revealed there was no significant difference in the proliferation of EPC between AQP1 WT and KO group mice. Transwell assay showed that EPC migration ability of AQP1 KO mice was significantly weaker than that of WT mice. The scratch healing ability of EPC in AQP1 KO mice was significantly lower than that of WT mice.ConclusionsEPC initially shows the characteristics of stem cells and with the prolongation of culture time, EPC gradually shows the characteristics of endothelial cells. AQP1 affects the EPC migration rather than proliferation.
Objective To investigate the changes of renal medulla aquaporin 2 expression and morphological changes of epithelia of collecting tube after bile duct recanalizaiton operation. Methods Thirty rats were divided into two groups randomly. Common bile duct ligation was performed on 20 experimental rats with silicon tubes 2 mm in extre-diameter, and sham operation on the other 10 rats. Seven days later, bile duct recanalizaiton was performed on obstructive jaundice group and sham operation on contrast group. Experimental rats were divided into two subgroups randomly. Half of them were killed immediately and the others would be killed 24 hours later. Serum of each rat was collected to detect hepatic function and renal function. Renal medulla was fixed for microscopic examination and was kept in the -80 ℃ refrigerator for aquaporin 2 expression measurement by Western blot technique. Results All of the animals accomplished the experiment smoothly. Golden ascites were found in the rats of obstructive jaundice group. Twenty-four hours after recanalization, serum bilirubin levels decreased 〔(45.95±8.39) μmol/L〕, P＜0.01, and there was no significant change in blood urine and creatine level. Compared with sham operation group (21 966.20±1 544.70), expression of aquaporin 2 decreased significantly after common bile duct ligation in obstructive jaundice group (15 665.30±1 181.85), P＜0.01. After recanalizaion, the expression of aquaporin 2 in obstructive jaundice group increased (19 490.80±4 239.32), P＜0.01. Conclusion Common bile duct obstruction would lead to epithelium injury of renal collecting tube, and down regulate the aquaporin 2 expression.
Neuromyelitis spectrum disease (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system. The breakdown of the blood-brain barrier (BBB), as an important link in the pathogenesis of NMOSD, has an important impact on the occurrence, development and prognosis of the disease. It is generally believed that the aquaporin 4 antibody produced in the peripheral circulation crosses the BBB cause damage to the central nervous system, and there are components involved in the destruction of BBB in the occurrence and development of NMOSD disease. At present, little is known about the molecular mechanism of BBB destruction in NMOSD lesions and there is still a lack of systematic theory. Further research and exploration of the regulatory mechanism of BBB permeability and the manifestation of barrier destruction in NMOSD diseases are of great significance for understanding the pathogenesis of NMOSD, so as to achieve early diagnosis and discover new therapeutic and preventive targets.
