Delayed macular hole secondary to Terson syndrome: a case report and literature review.

Terson syndrome refers to intraocular haemorrhage that occurs due to subarachnoid bleeding associated with an acute increase in intracranial pressure. No previous study has reported a delayed macular hole (MH) secondary to Terson syndrome. A 17-year-old boy visited our department and presented with vitreous bleeding and a history of subarachnoid haemorrhage. Sub-internal limiting membrane (ILM) haemorrhage with ILM detachment and intraretinal haemorrhage were detected during pars plana vitrectomy. Additionally, a delayed MH was detected 1 week after the surgery. There was no sign of MH closure during a 2-month follow-up. Subsequently, an MH massage was performed to close the MH. Our findings suggest that a delayed MH can occur secondary to Terson syndrome. Elevated hydrodynamic pressure and hydrostatic pressure, which are caused by sub-ILM and intraretinal haemorrhages of the fovea, contribute to the formation of an MH. Additionally, ILM peeling may cause damage to the macula and facilitate the formation of MHs. Although the MH may close by itself, early surgical intervention is recommended when there is no sign that the MH will close spontaneously because a prolonged MH can lead to retinal damage.

A Case of Cerebral Large-Vessel Vasculitis Concomitant Fahr Syndrome in Systemic Lupus Erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogenous, devastating autoimmune inflammatory disease with multiorgan involvement. A variety of neurological and psychiatric symptoms may be caused by nervous system involvement, termed neuropsychiatric systemic lupus erythematosus. CASE REPORT: We describe a young man newly diagnosed with SLE who had a stroke as an initial symptom and was found to have cerebral large-vessel vasculitis and Fahr syndrome. CONCLUSIONS: The novelties of this report are the extensive cerebral calcification demonstrated on head computerized tomography in a patient with SLE, and the depiction of an underlying vasculitis on high-resolution magnetic resonance vessel wall imaging. It is our aim to describe this atypical form of neuropsychiatric systemic lupus erythematosus onset and to make known the usefulness of the new magnetic resonance imaging techniques for the diagnosis of cerebral large-vessel vasculitis.

CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

PURPOSE: To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. METHODS: A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. RESULTS: Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). CONCLUSION: The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

The correlation between peripheral complete blood count parameters and diabetic macular edema in proliferative diabetic retinopathy patients: a cross-sectional study.

Background: Numerous studies have demonstrated that retinal chronic inflammation plays a critical role in the pathogenesis of diabetic macular edema (DME). However, studies about the association between peripheral complete blood count, an inexpensive and easily measurable laboratory index, and DME are limited. Research design and methods: The current study was a hospital-based, cross-sectional study. The participants were inpatients with type 2 diabetes who underwent vitrectomy for PDR, and the contralateral eyes in these PDR patients meeting the criteria were included in the study. Central macular thickness (CMT) was measured automatically and the DME was characterized as CMT ≥ 300 µm. Results: A total of 239 PDR participants were enrolled. The average age was 55.46 ± 10.08 years old, and the average CMT was 284.23 ± 122.09 µm. In the fully adjusted model, for CMT, the results revealed a significantly negative association between CMT and both white blood cell (WBC) count and neutrophil count (ß = -11.95, 95% CI: -22.08, -1.82; p = 0.0218; ß = -14.96, 95% CI: -28.02, -1.90; p = 0.0259, respectively); for DME, the results showed an inverse association between DME and WBC count, monocyte count, and eosinophil count (OR = 0.75, 95% CI: 0.59, 0.95; p = 0.0153; OR = 0.07, 95% CI: 0.00, 0.92; p = 0.0431; OR = 0.03, 95% CI: 0.00, 0.88; p = 0.0420, respectively). Conclusions: In conclusion, our results suggest that WBC and its subtypes in circulation may play an important role in the pathogenesis of DME in PDR patients.

Interleukin-6 in retinal diseases: From pathogenesis to therapy.

Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in immunomodulation, inflammation, increases vascular permeability, hematopoiesis, and stimulates cell proliferation, among other biological processes. It exerts effects primarily through the classic and trans-signaling pathways. Many studies have demonstrated that IL-6 plays a critical role in the development of retinal diseases including diabetic retinopathy, uveitis, age-related macular degeneration, glaucoma, retinal vein occlusion, central serous chorioretinopathy and proliferative vitreoretinopathy. Thus, the progressive development of drugs targeting IL-6 and IL-6 receptor may play a role in the treatment of multiple retinal diseases. In this article, we comprehensively review the IL-6's biological functions of and its mechanisms in the pathogenesis of various retinal diseases. Furthermore, we summarize the drugs targeting IL-6 and its receptor and prospect their potential application in retinal diseases, hoping to provide new ideas for the treatment of retinal diseases.

Clinical features and therapeutic management of choroidal osteoma: A systematic review.

Choroidal osteoma is a benign ossifying tumor within the choroid. Complications associated with choroidal osteoma, including disruption of retinal pigment epithelium, atrophy of photoreceptors, subretinal fluid, and choroidal neovascularization, present challenges for clinicians, and management remain controversial. We performed a comprehensive search in the PubMed, EMBASE, and Ovid databases for published studies and case reports relating to the management of choroidal osteoma. Since it was first described in 1978, various case reports of ocular complications associated with choroidal osteoma have been documented, and various therapies have yielded different outcomes. We systematically evaluate the literature published on this rare entity.

The association between different hypoglycemic regimens and postoperative diabetic macular edema after vitrectomy in the Japanese patients with proliferative diabetic retinopathy.

Purpose: To study the association between different hypoglycemic regimens and postoperative diabetic macular edema (DME). Methods: A secondary analysis based on a retrospective cohort study. Results: In this secondary analysis, 124 eyes from patients with proliferative diabetic retinopathy (PDR) who underwent pars plana vitrectomy (PPV) between January 2008 and September 2012 were included. We found that compared with oral hypoglycemic medication, oral hypoglycemic medication plus insulin treatment revealed an insignificant relationship with postoperative DME (odds ratio [OR]=0.8, 95% confidence interval [CI]: 0.12-5.21, P=0.8167), only insulin treatment revealed a significant association with postoperative DME (OR=0.10, 95% CI: 0.01-0.84, P=0.0337) after adjusted age, sex. After adjusted age, sex, diabetes mellitus (DM) duration, glycosylated hemoglobin (HbA1c), the results did not have obvious changes (OR=0.61, 95% CI: 0.09-4.26, P=0.6187; OR=0.07, 95% CI: 0.01-0.65, P=0.0197). Furthermore, after adjusted age, sex, DM duration, HbA1c, hypertension, intraoperative retinal photocoagulation, vitreous hemorrhage, macular detachment, fibrovascular membrane, intraocular lens implantation and microincision vitrectomy surgery, the results were consistent (OR=0.66, 95% CI: 0.05-9.49, P=0.7621; OR=0.06, 95% CI: 0.00-0.81, P=0.0342). The same trend was observed in these adjusted models as well (p for trend was 0.0254, 0.0141, and 0.0311, respectively). Conclusion: In conclusion, our results of the secondary analysis should be interpreted as a significant association between insulin treatment and reduced risks of postoperative DME in Japanese PDR patients with PPV surgery, compared with oral medications. Well glycemic control with longstanding insulin therapy may be beneficial to reduce the risks of postoperative DME in PDR patients. Our investigation calls for large-scale and long-term prospective clinical studies for a full evaluation of the exact role of insulin in the progression of postoperative DME.

HMGB1/TLR4 induces autophagy and promotes neuroinflammation after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) causes autophagy as well as inflammation; the latter is known to involve the high-mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4) axis. Here we investigated whether this axis may help mediate both the autophagy and inflammation associated with ICH. METHODS: ICH was induced by injecting autologous blood into Sprague-Dawley rats, followed in some cases by intracerebroventricular injection of short interfering RNA (siRNA) against HMGB1 or TLR4 at 6 h after ICH induction or by intraperitoneal injection of the autophagy inhibitor 3-methyladenine (3-MA) or autophagy activator rapamycin at 6, 24, and 48 h after ICH induction. Western blotting, immunohistochemistry or immunofluorescence was used to assess levels of HMGB1/TLR4 signaling pathway proteins as well as markers of autophagy (LC3B, Beclin1, Atg5) or inflammation (IL-1 beta, TNF-α). Numbers of apoptotic cells were determined using TUNEL staining. Changes in levels of these proteins were correlated with neurological deficits measured using the modified Neurological Severity Score. RESULTS: ICH caused HMGB1 to translocate from the nucleus into the cytoplasm, and it up-regulated expression of TLR4 and myeloid differentiation factor 88 (MyD88), and induced neurological deficits. Administering siRNA against HMGB1 or TLR4 reversed this up-regulation. Levels of markers of autophagy (LC3B, Beclin1, Atg5) or inflammation (IL-1 beta, TNF-α) were significantly higher 72 h after ICH than at baseline, as were the numbers of TUNEL-positive cells. Administering siRNA against HMGB1 or TLR4 markedly alleviated inflammation, and autophagy, apoptosis, and neurological deficits. Similarly, administering autophagy inhibitor 3-MA alleviated inflammation, apoptosis, and neurological deficits. Conversely, autophagy activator rapamycin exacerbated these effects of ICH. CONCLUSIONS: During the acute phase of ICH, the HMGB1/TLR4/MyD88 axis acts via autophagy to promote inflammation.

CircRNA CTNNB1 (circCTNNB1) ameliorates cerebral ischemia/reperfusion injury by sponging miR-96-5p to up-regulate scavenger receptor class B type 1 (SRB1) expression.

Emerging studies show that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. The present study discovered that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in mouse astrocytes (mAS) treated with oxygen glucose deprivation and reperfusion (OGD/R), and similar results were observed in a mouse middle cerebral artery occlusion model. Overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and the inflammatory response induced by OGD/R in vitro. Up-regulation of circCTNNB1 increased SRB1 expression levels to protect mAS cells from OGD/R-induced damage. CircCTNNB1 and SRB1 interacted with miR-96-5p, and the overexpression of miR-96-5p efficiently reversed the function of circCTNNB1 in OGD/R-treated mAS cells. CircCTNNB1 protected against cerebral ischemia-reperfusion injury by up-regulating SRB1 in vivo. In conclusion, our findings suggest that circCTNNB1 acts as a competitive endogenous RNA for miR-96-5p to alleviate cerebral IRI, which provides novel evidence that circCTNNB1 and SRB1 may be biomarkers and therapeutic targets for cerebral IRI.

Relationship between renal function and prognosis of Chinese proliferative diabetic retinopathy patients undergoing the first vitrectomy: protocol for a prospective cohort study.

INTRODUCTION: China has the largest number of adults with diabetes aged 20-79 years (116.4 million) in 2019. Due to the socioeconomic condition or a lack of awareness of diabetic complications, many adults with diabetes have proliferative diabetic retinopathy (PDR) or renal function impairment at their first visit to the clinic for a sudden loss of vision, and pars plana vitrectomy (PPV) is required for their treatment. Risk factors for the outcomes and complications of PPV surgery in PDR patients have been widely explored in many epidemiological studies and clinical trials. However, few prospective studies have analysed the association between renal function and surgical outcomes in PDR. METHODS AND ANALYSIS: This is a single-centre, prospective cohort study of PDR patients with type 2 diabetes mellitus who have definite indications for PPV surgery with or without renal function impairment. We will consecutively enrol PDR patients who meet the inclusion and exclusion criteria from November 2020 to December 2023. Each participant will be followed up for at least 6 months after surgery. Clinical data from medical records and vitreous fluid will be collected.Demographic characteristics and study outcomes will be summarised using descriptive statistics. The variation will be described and evaluated using the χ² test or Kruskal-Wallis test. Generalise additive mixed models will be used to explore the association between the renal profile and surgical outcomes including BCVA, and retinal and choroidal microvasculature/microstructure. Multivariate ordinal regression analysis will be used to detect the independent association between renal profile and BCVA changes, and smooth curve fitting will be employed to briefly present the tendency. ETHICS AND DISSEMINATION: The trial has received ethical approval from the West China Hospital of Sichuan University. Results of this trial will be disseminated through publication in peer-reviewed journals and presentations at local and international meetings. TRIAL REGISTRATION NUMBER: ChiCTR2000039698.

Intravitreal Injection of Amyloid ß1-42 Activates the Complement System and Induces Retinal Inflammatory Responses and Malfunction in Mouse.

To investigate whether intravitreal injection of amyloid ß1-42 (Aß1-42) activates the complement system and induces retinal inflammatory responses and malfunction, Aß1-42 was applied intravitreally in mice. The expressions of key components of complement system were determined by real-time PCR. Retinal function was assessed by electroretinography. We found interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in Aß1-42 treated mice retinas increased from day 1 to day 7. Compared with control group, mRNA expression of C1qa and C3 in the Aß1-42 treated retinas increased at days 1 and 7. The level of CFB, CFD, or CFH increased at day 4 and day 7. Regulator of membrane attack complex (MAC), CD59a, increased from day 1 to day 7. The expression of the main complement components in Aß1-42 treated eyes increased at days 4 and 7. Therefore, our results suggested that exogenous Aß1-42 activated CP and AP of the complement system in mice retinas, induced retinal inflammatory responses, and caused retinal malfunction.

Sex-Specific Differences in Clinical Characteristics and Outcomes Among Patients with Vascular Abnormality-Related Intracerebral Hemorrhage.

BACKGROUND: Results are conflicting as to whether sex has an impact on the outcome of intracerebral hemorrhage (ICH), especially when etiologies differ. In this study, we investigated whether sex differences exist in patients with vascular abnormality-related ICH. METHODS: Patients (age ≥18 years) diagnosed with ICH within 7 days of symptom onset were admitted consecutively between January 2012 and February 2014 from 50 hospitals across mainland China. Vascular abnormality related to ICH included aneurysm, arteriovenous malformation, moyamoya disease, and cavernous malformation. The outcomes were death and death/disability at 3 months. Disability was defined as modified Rankin Scale score >2. Multivariable logistic regression was used to estimate the association between sex and outcome. RESULTS: Women accounted for 41.9% (170) of the 406 patients, and they tended to be older than the men (women: 43.5 ± 19.3 years; men: 40.0 ± 17.7 years; P = 0.056). The proportions of ICH-related vascular abnormalities were as follows: aneurysm, 32% (130/406); arteriovenous malformation, 50.3% (204/406); moyamoya disease, 11.3% (46/406); and cavernous malformation, 6.4% (26/406). After we adjusted for age, National Institute of Health Stroke Scale, Glasgow Coma Scale score, location of hemorrhage, and surgery, female sex remained an independent predictor of death/disability at 3 months (odd ratio 2.49, 95% confidence interval 1.31-4.75), but not for death alone (odd ratio 1.45, 95% confidence interval 0.58-3.61). CONCLUSIONS: In our study, female sex was an independent risk factor for poor outcomes in patients with vascular abnormality-related ICH. The factors contributing to this sex difference should be investigated in the future.

Expression of galectin-3 and apoptosis in placental villi from patients with missed abortion during early pregnancy.

The success of a pregnancy relies on moderate trophoblast apoptosis. If the 'inhibition-induction' balance of apoptosis is broken, a pathological pregnancy may occur. Galectin-3 has an important role in numerous biological processes, including tumor cell apoptosis. However, the association between galectin-3 and missed abortion (MA) has remained elusive. In the present study, the mRNA and protein expression levels of galectin-3 in placental villi, and the apoptotic index of placental cells from patients with MA were assessed and compared with those in a normal spontaneous abortion group. The present study investigated the function of galectin-3 in the process of MA and the possible association between placental apoptosis and galectin-3 expression in MA patients. Furthermore, the role of galetin-3 in patients with MA at different times (<4 and >4 weeks) was explored. The present study provided a potential mechanism of MA from a perspective of apoptosis and also provided potential therapeutic approaches to prevent MA.

Activation of liver X receptor α protects amyloid ß1-40 induced inflammatory and senescent responses in human retinal pigment epithelial cells.

OBJECTIVE: To investigate whether activation of the liver X receptors (LXRs) inhibits amyloid ß1-40 (Aß1-40) induced inflammatory and senescent responses in human retinal pigment epithelial (RPE) cells. MATERIALS AND METHODS: Confluent cultures of human primary RPE and ARPE-19 cells pretreated with 5 µΜ of TO901317 (TO90), a synthetic agonist of LXR, or vehicle were incubated with 1 µΜ of Aß1-40 or Aß40-1. The optimum concentrations of Aß1-40 and TO90 were determined by cell viability assay. Pro-inflammatory cytokines IL-6, IL-8, MCP-1 were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Expression and localization of an aging protein p16INK4a (p16) were analyzed by western blotting and immunofluorescence. Expressions of LXRs and one of their target genes ATP-binding cassette transporter A1 (ABCA1) were examined by real-time PCR and western blotting. Phosphorylated transcription inhibition factor-κB-α (p-IκB-α) was assessed by western blotting. RESULTS: A negative linear relationship between the Aß1-40 concentration and the cell viability was evident, indicating Aß1-40 decreased ARPE-19 cell viability in a dose-dependent manner. Aß1-40 enhanced the expression of IL-6, IL-8, MCP-1 as well as p16 in both RPE cell lines at both mRNA and protein levels, whereas TO90 counteracted the detrimental effects. TO90 upregulated the expression of LXRα and its target gene ABCA1, but it did not affect the expression of LXRß. Meanwhile, TO90 inhibited the phosphorylation of IκB-α mediated by Aß1-40 stimulation. CONCLUSION: Activation of the LXRα-ABCA1 axis may alleviate Aß1-40 induced inflammatory and senescent responses in RPE cells. The beneficial effect appears associated with the inhibition of the NF-κB signaling pathway.

A safety study of high concentration and high frequency intravitreal injection of conbercept in rabbits.

The novel anti-VEGF drug conbercept has been used in the treatment of several retinal neovascular diseases. Owning to the alteration of the structure, the newest drug is capable of combining more molecular targets and present higher affinity to the angiogenesis promoting factors. However, it is unknown whether it will cause any unwanted effects like other anti-VEGF agents. We studied the short-term safety of high concentration and high frequency intravitreal injection of conbercept in rabbits. Intraocular pressure, fundus-photography, ERGs were applied. Retinal morphology, the amount of apoptotic cells and protein levels of IL-6, IL-8 and TNF-α in the aqueous humor were determined. Retinal proteomics was detected using tandem mass tags (TMTs) quantitative mass spectrometry. The difference of IOP, ERGs, protein levels of inflammatory factors among rabbits received conbercept and PBS was not significant (P > 0.05). Fundus photographs and retinal morphology of animals in the conbercept-injected groups mimic those observed in the PBS-injected groups. No TUNEL-positive cell was seen in the retinal ganglion cell layer in the conbercept-injected groups. Proteomics did not show significant changes of inflammation or apoptosis associated proteins in the conbercept-injected eyes. We conclude that intravitreal injection of high concentration and high frequency conbercept is well tolerated at least in a short-term in rabbits.

AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways.

Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1-7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1-7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1-7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases.

Etiology, clinical characteristics and prognosis of spontaneous intracerebral hemorrhage in children: A prospective cohort study in China.

BACKGROUND AND OBJECTIVE: Much is known about spontaneous intracerebral hemorrhage (SICH) in adults, but few studies have examined pediatric SICH, especially in China. The aim of the present study was to describe the etiology, clinical characteristics and prognosis of SICH in children from southwest China. METHOD: Consecutive patients aged 1-18 years with SICH at our medical center were prospectively enrolled from January 2012 to June 2014. SICH was defined by WHO criteria and confirmed by CT or MRI findings. Demographic and clinical information was collected at baseline, and follow-up assessments were conducted at 3 and 6 months after SICH, when patients were scored on the modified Rankin Scale (mRS) and events of deaths and recurrent hemorrhagic stroke were recorded. RESULTS: Among the 70 children (43 males; median age, 12.0 years) in the final analysis, 44 patients (62.9%) had SICH due to arteriovenous malformation, and less frequent etiologies were cavernous malformation (n=4), aneurysm (n=2), tumors (n=2), moyamoya (n=2), hemophilia (n=1), hypertension (n=1), while 14 (20.0%) had SICH of unknown etiology. The mortality rate at 3 months and 6 months was equal, which was both 3%. The rate of disability was 12.1% at 3 months and 9.1% at 6 months. CONCLUSION: The most frequent etiology of pediatric SICH in this Chinese cohort was arteriovenous malformation. SICH of unknown etiology occurred much more often in our cohort than in previously published Caucasian patients in the US and Europe.

Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-κB pathways in ARPE-19 cells.

Oxidative stress and inflammation are two interrelated biological events implicated in the pathogenesis of many diseases. Reactive oxygen species (ROS) produced under oxidative stress play a key role in pathological conditions. Inhibition of p22phox, an indispensable component of the NADPH oxidase (NOX) complex comprising the main source of ROS, plays a protective role in many ocular conditions by inhibiting the activation of NOXs and the generation of ROS. However, little is understood regarding the role of p22phox in oxidative stress-related inflammation in the eye. We used a p22phox small interfering RNA (siRNA) to transfect the retinal pigment epithelium (RPE)-derived cell line ARPE-19, and human primary RPE (hRPE) cells, then stimulated with Ang II. We observed a potent anti-inflammatory effect and studied the underlying mechanism. Downregulating p22phox resulted in decreased ROS generation, a reduction of NOXs (NOX1, 2, 4) and a decrease in inflammatory cytokine. In addition, p22phox downregulation reduced the activation of the MAPK and NF-κB signaling pathways. We conclude that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced oxidative stress. Suppressing the MAPK and NF-κB pathways is involved in this protective effect. These results suggest that p22phox may provide a promising therapeutic target for oxidative stress-induced ocular inflammation.

Differences Between Vascular Structural Abnormality and Hypertensive Intracerebral Hemorrhage.

BACKGROUND: How the clinical characteristics and prognosis of various types of vascular structural abnormality-related intracerebral hemorrhage (ICH) differ from those of hypertensive ICH is poorly understood. This lack of understanding poses a problem for differential diagnosis and prognosis. METHODS: Patients diagnosed with ICH between January 2012 and February 2014 at 50 tertiary and secondary hospitals in China were enrolled into this prospective cohort study. Patients were classified as having vascular structural abnormality-related ICH or hypertensive ICH, and data on the demographics and clinical characteristics of each group were compared. Multivariate logistic regression was used to explore associations while controlling for other risk factors for good outcome and mortality. RESULTS: Data for 281 patients showed that vascular structural abnormality-related ICH usually occurred in lobar areas and affected patients who were younger and had higher Glasgow Coma Scale (GCS) scores than those with hypertensive ICH. Mortality and good outcome at 3 months after ICH were significantly better among patients with vascular structural abnormality-related ICH (3.4% and 77.2%) than among patients with hypertensive ICH (15.2% and 49.9%, both P < .001). Multivariate logistic regression identified the following independent predictors of mortality: lower GCS score, old age, presence of intraventricular hemorrhage, larger hematoma volume, and surgery treatment. The regression also identified several independent predictors of good outcome at 3 months: ICH etiology due to vascular structural abnormality, higher GCS score, younger age, and smaller hematoma volume. CONCLUSIONS: Patients with vascular structural abnormality-related ICH are more likely to experience better clinical outcomes than those with hypertensive ICH. GCS score, age, hematoma volume, and ICH etiology are independent predictors of ICH outcome.

Topical administration of diminazene aceturate decreases inflammation in endotoxin-induced uveitis.

PURPOSE: Our previous study demonstrated that an intraperitoneal injection of Diminazene Aceturate (DIZE) attenuated uveitis by activating ocular angiotensin-converting enzyme 2 (ACE2). Here, we investigated the anti-inflammatory effects on the ocular anterior segment of a topical administration of a DIZE solution and explored the downstream target molecules involved in the anti-inflammatory mechanism after ACE2 activation. METHODS: Endotoxin-induced uveitis (EIU) in rats was induced by a subcutaneous injection of lipopolysaccharides (LPS, 200 µg) in 0.1 ml of sterile saline. DIZE (0.025, 0.05, or 0.1%) and dexamethasone (0.1%) solutions were applied topically (10 µl eyedrops) to both eyes 6X every two hours before and after LPS injection. The inflammation of the ocular anterior segment was observed and the clinical scores were evaluated 24 h after LPS injection. The total protein concentration and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the aqueous humor were determined. CD11b-positive cells adjacent to the iris ciliary body (ICB) were stained by immunohistochemistry. The mRNA levels of inflammatory cytokines and mediators, including IL-1ß, TNF-α, COX-2, and iNOS or NF-κB subunit p65 in the ICB, were analyzed by real time RT-PCR. The protein expression of NF-κB p65 and the phosphorylated protein of p38 MAPK were detected by western blotting. RESULTS: A topical administration of DIZE decreased clinical scores and the total protein concentration, as well as TNF-α and IL-6 levels in the aqueous humor. Meanwhile, the mRNA levels of inflammatory cytokines and mediators, including IL-1ß, TNF-α, COX-2, and iNOS in the ICB, were downregulated. DIZE reduced the recruitment of CD11b-positive cells adjacent to the ICB. Furthermore, DIZE downregulated the expressions of NF-κB subunit p65 at protein and mRNA levels and inhibited the phosphorylation of p38 MAPK protein in the ICB. CONCLUSIONS: A topical administration of DIZE suppressed ocular inflammation in EIU and decreased the levels of inflammatory cytokines. DIZE attenuated the activation of NF-κB and p38 MAPK in EIU, which may be associated with ACE2-mediated anti-inflammatory effects. Our data provided further evidence that DIZE may represent a novel class of drug for the management of ocular inflammation.