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The aim of this study was to assess the mechanism of vitamin A combined with regenerated oxidationreducing nanomedicine in treating rats with dry eyes. Sprague Dawley (SD) rats were divided into control set, Dry eye disease (DED) set, VA set, CeO2 NPs set and combined set. The model of DED rat was prepared through injection with Scopolamine Hydrobromide and quantity of tear fluid was detected. The breakup time (BUT) was detected with fluorescein sodium test paper, and degree of corneal injury was evaluated with fluorescein sodium staining method. The change of superoxide dismutase (SOD) activity and reactive oxygen species (ROS) content was analyzed and secretion of IL-6 and IL-1β in serum was tested with enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of Bcl-2 and Bax were analyzed with Western Blot assay and quantity of tear fluid in the treated sets was increased and BUT was lengthened. The corneal injury was improved, and ROS content was reduced and SOD activity increased. The secretion of IL-6 and IL-1β was reduced. Moreover, Bcl-2 expression was increased, while Bax expression was reduced. The action in combined set was more notable and DED was treated by vitamin A combined with regenerated oxidationreducing nanomedicine through improving oxidative stress and restraining the inflammatory secretion. The apoptosis could be regulated.

AIM: To present the clinical manifestations of 5 autosomal dominant cone-rod dystrophy (adCORD) patients from two Chinese families with cone-rod homeobox (CRX) mutation (p.R41W), and to explore the clinical heterogeneity of adCORD with CRX mutation (p.R41W). METHODS: Interrogation and ophthalmological examinations were undertaken in all patients and unaffected members. Analysis of clinical features was performed by visual acuity, slit lamp examination, visual field examination, fundoscopy, autofluorescence and spectral domain optical coherence tomography. Targeted next-generation sequencing was applied as a useful tool to identify the causative mutation of CORD genes. RESULTS: A CRX missense mutation c.121C>T was identified in all patients, resulting in an amino acid change from arginine acid to tryptophan (p.R41W). The patients presented with early onset, progressive and different severities with CORD. CONCLUSION: This is the first report of the clinical phenotype of CRX mutation (p.R41W) in Chinese families, and the mutation can lead to a wide range of various retinal phenotypes.

Purpose: The aim of this study is to examine whether or not myocilin (MYOC) genetic variations are associated with susceptibility to primary angle-closure glaucoma (PACG) in the Han Chinese population. Methods: Four single-nucleotide polymorphisms (SNPs)—rs235913, rs183532, rs12076134, and rs235875—in the MYOC gene were genotyped in 212 adult patients with PACG and 255 age-, sex-, and ethnic-matched healthy controls by using a polymerase chain reaction–restriction fragment length polymorphism assay. Data were analyzed by chi-square analysis. Results: The four SNPs in the MYOC gene were in the Hardy–Weinberg equilibrium in all the subjects. The frequencies of A allele rs183532 were significantly different between the PACG patients and the controls (0.238 vs. 0.169, p=0.008; OR=1.541; 95% CI: 1.117–2.127). The frequencies of the AA genotype and A allele of rs235913 were increased in PACG patients compared with controls, but the difference was not significant (p=0.037, p=0.017, respectively). A comparison of the distributions of the genotypes and alleles of rs12076134 and rs235875 showed no statistically significant differences between the PACG patients and the controls (p>0.05). Haplotype analysis indicated that the frequency of the AATG and AATA haplotypes was significantly higher for PACG patients than for control subjects (both p

BACKGROUND Intraoperative magnetic resonance imaging (iMRI) combined with optic radiation neuronavigation may be safer for resection of cerebral lesions involving the optic radiation. OBJECTIVE To investigate whether iMRI combined with optic radiation neuronavigation can help maximize tumor resection while protecting the patient's visual field. METHODS Forty-four patients with cerebral tumors adjacent to the optic radiation were enrolled in the study. The reconstructed optic radiations were observed so that a reasonable surgical plan could be developed. During the surgery, microscope-based fiber tract neuronavigation was routinely implemented. The lesion location (lateral or not to the optic radiation) and course of the optic radiation (stretched or not) were categorized, and their relationships to the visual field defect were determined. RESULTS Analysis of the visible relationship between the optic radiation and the lesion led to a change in surgical approach in 6 patients (14%). The mean tumor residual rate for glioma patients was 5.3% (n = 36) and 0% for patients with nonglioma lesions (n = 8). Intraoperative MRI and fiber tract neuronavigation increased the average size of resection (first and last iMRI scanning, 88.3% vs 95.7%; P < .01). Visual fields after surgery improved in 5 cases (11.4%), exhibited no change in 36 cases (81.8%), and were aggravated in 3 cases (6.8%). CONCLUSION Diffusion tensor imaging information was helpful in surgical planning. When iMRI was combined with fiber tract neuronavigation, the resection rate of brain lesions involving the optic radiation was increased in most patients without harming the patients' visual fields.

A novel compound mutation in CNGA1 gene, coding for the cGMP-gated ion channel protein, results in a protein product that is not targeted to the plasma membrane, which would be deleterious to rod photoreceptors leading to retinitis pigmentosa (RP)., Retinitis pigmentosa (RP) describes a group of inherited retinopathies that are characterized by the progressive degeneration of photoreceptor neurons, which causes night blindness, a reduction in the peripheral visual field and decreased visual acuity. More than 50 RP-related genes have been identified. In the present study, we analysed a Chinese family with autosomal recessive RP. We identified a compound heterozygous mutation, c.265delC and c.1537G>A, in CNGA1 using targeted next-generation sequencing (NGS) of RP-causing genes. The mutations were validated in the family members by Sanger sequencing. The mutations co-segregated with the RP phenotype and were absent from ethnically-matched control chromosomes. The mutant (mut) CNGA1 p.(G513R) protein caused by the mis-sense novel mutation c.1537G>A was expressed in vitro. The mut CNGA1 p.(G513R) protein was largely retained inside the cell rather than being targeted to the plasma membrane, suggesting the absence of cGMP-gated cation channels in the plasma membrane would be deleterious to rod photoreceptors, leading lead to RP.

This study investigated whether functional neuronavigation can be used to remove lesions in the lateral ventricle while preserving patients' neurologic functionality.A total of 60 patients with lateral ventricular meningiomas were divided into study and control groups (n = 30 each). Diffusion tensor and blood oxygenation level-dependent functional magnetic resonance imaging were used for fiber tracking and eloquent cortex localization, respectively, in the study group. The surgical approach was based on coregistered data sets from 3-D lesion and brain structure reconstructions. Patients in the control group underwent anatomic neuronavigation-guided surgery. The patients' demographics, degree of resection, visual field, language score, movement, preoperative and postoperative Karnofsky Performance Status (KPS) scores, and surgical complications were recorded.Tumors were completely removed in both groups. Patients in the study group had a higher rate of visual field preservation than controls (P = 0.01). The two groups had similar motor and language functions after surgery, except that fewer cases of transient aphasia were observed in the former (P0.05). KPS scores for the study and control groups were 80 (70-80) and 70 (60-70), respectively (P0.01), at 2 weeks and 90 (80-100) and 85 (70-90), respectively (P = 0.022), at 3 months after surgery.Functional neuronavigation preserved neurologic functionality and was especially beneficial for protecting optical functionality and for the rapid recovery of patients.

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-1β 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-1β 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.

Adeno-associated virus vector plasmid carrying the expression cassette of brain-derived neurotrophic factor (BDNF), pAAV-BDNF, was constructed and packaged into recombinant adeno-associated virus (rAAV-BDNF). The rAAV-BDNF was intravitreally injected into streptzotocin (STZ)-induced diabetic Sprague–Dawley (SD) Rats. Data showed that over-expression of BDNF could increase alive retinal ganglion cell (RGC) number and improve its function in streptzotocin(STZ)-induced diabetic rats, which might be a new method to treat diabetic neuropathy and retinopathy.

Background: Eales' disease (ED) is an idiopathic obliterative vasculopathy that usually affects the peripheral retina of young adults. The aim of this study is to investigate Th1/Th2 serum cytokine profiling in patients with ED. Methods: This study included 30 male patients with ED and 10 healthy controls. The ED patients were divided into two subgroups: the vitreous haemorrhage (VH) group (n = 18) and non-vitreous haemorrhage (NVH) group (n = 12). Sixteen patients (six from the VH group and 10 from the NVH group) received glucocorticoid treatment for three months and were followed for six months. Levels of six cytokines including interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and four interleukins (IL-2, IL-4, IL-5 and IL-10) in the serum samples were determined by Luminex assays. Results: Compared to controls, ED patients showed significantly higher levels of IL-10 and TNF-α, increased IFN-γ/IL-4 (Th1/Th2) ratio, and lower levels of IL-4 (p < 0.05). Glucocorticoid treatment caused a restoration in the cytokine levels and the IFN-γ/IL-4 ratio. Multivariate analysis revealed that reduced IL-4 (less than 4 pg/ml) and elevated IL-10 (greater than 4 pg/ml) levels were independent predictors of ED with odds ratios of 0.024 (95% CI, 0.002–0.255; p = 0.002) and 12.108 (95% CI, 1.045–140.233; p = 0.046), respectively. Conclusion: The findings demonstrate for the first time that there is an imbalance of Th1/Th2 cytokines in ED patients, which can be reversed by glucocorticoid treatment. Additionally, both IL-4 and IL-10 might represent potential diagnostic markers for the disease.

To probe the intervention and mechanism of the inhibitor of heparanase (PI-88) on the experimental CNV model .Experimental CNV was induced by laser photocoagulation in 29 mail (Brown Norway) BN rats (647 nm wave length Krypton laser, 360 mW power, 50 microm spot size, 0.05 second duration), and randomly divided into vacant control group, physiologic saline control group, preventive group and treated group, another 3 rats were acted as normal group, 15 days continuous intraperitoneal injection of PI-88 (25 mg kg(-1) d(-1) was administrated in preventive group (PI-88 was administered the same day as photocoagulation) and treated group (PI-88 was administered 1 week after photocoagulation when CNV had been formed), for the physiologic saline control group, PI-88 was replaced by physiologic saline. To comprehensively evaluate the effect of PI-88 on the CNV by the quantitation of CNV area marked by FITC-dextran in choroid-sclera flat mounts, fluorescence fundus angiography and histopathology; the changes of HPA expression were surveyed by western blot and immunohistochemistry.CNV area of preventive group and treated group decreased 52.1% and 53.8% respectively at the time point of 3 weeks after photocoagulation; the relative thickness of CNV membrane in eyes of treated group had been decreased 46% as that of control group by histopathology; CNV occurrenced 1 week after photocoagulation both in the control group and preventive group, while the fluorescein leakage of the preventive group had been inhibited significantly; 3 weeks after photocoagulation, there had been 7 days discontinuation for the prevent group, the fluorescein leakage did not enhanced, while there had been 15 days continuous administration for the treated group, the fluorescein leakage had been decreased significantly compared to the time point of 2 week; western blot showed that the relative expressed levels of HPA protein in both preventive and treated group decreased; HPA displayed distribution at the leading edge of CNV membrane migrating toward inner retina and the vascular tissue by immunohistochemistry, the expression of HPA was inhibited significantly in treated group.PI-88 may not only prevent CNV in certain degree, but also make it partially subsidize for the existed CNV, and the effect is associated with the inhibition of HPA production.

To screen and identify the abnormal proteins expressed by hypoxia human retinal pigment epithelium (RPE) in vitro.It was a experimental study. Protein of normal/hypoxia human RPE cells in exponential phase of growth was extracted, and frozen by liquid nitrogen for proteome study. All samples were performed isoelectric focusing electrophoresis (IEF), separated by isoelectric point (pI); progressed sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE) and separated by protein molecular weight (Mr). 2D-gels revealed by coomassie brilliant blue, analyzed by Image Master 2D Elite. Differential proteins spots were screened in normal/hypoxia RPE cell. For identification of differential proteins, peptide masses were analyzed by matrix-assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF/MS).Five hundred and seventy-eight protein spots were obtained in normal group (matching rate within group was 92.90%), and hypoxia group 559 (91.41%). The average matching rate between two groups was 85.47%. There were 32 differential protein spots, which volume value changedor = 2.0 times. 7 spots were selected randomly for MS, and 5 proteins were identified successfully: HSP70 and HSP60 up-regulated; while beta-actin, beta-tubulin and peroxiredoxin 3 down-regulated.Findings of the in vitro study provide the evidence for expression changes of many proteins in RPE cell with hypoxia state; some of those regulated proteins can result in increasing stress capability obviously in cells, while the major cytoskeletal proteins down-regulated, and the ability of sustained-shapes, keeping order internal structure in cells decreasing. Proteome analysis provides a useful platform in systematic screening of various protein expressions in CNV related diseases.

The investigation of proteome can not only show the rules of vital movement, but also play an important role to illuminate the mechanism of genesis and development on certain diseases and that may find a new way to treat those. Using the compare analysis of proteome of physiology and pathology of individual, we can find the specific protein molecule of those diseases, provide identification markers of the diseases for early diagnosis, and point out the molecule target of the new drugs. Here we reviewed the applications of proteomic in the field of ophthalmologic research.

PURPOSE. To describe the electrophysiological, histologic, and hereditary features of a naturally occurring rat model of cone function loss. METHODS. Dark- and light-adapted electroretinograms (ERGs) were used to evaluate retinal function. The thickness and architecture of the retina were observed by light microscopy. The cone density was investigated by wholemount immunocytochemistry. The inheritance pattern was defined by mating with control female rats. RESULTS. In affected rats, light-adapted ERGs were nearly absent, whereas dark-adapted responses were of normal amplitude with delays in b-wave implicit time. Overall retinal structure was normal at the light microscopic level. There was no difference in cone density between control and affected rats. The cone function abnormality is inherited as an X-linked trait. CONCLUSIONS. A spontaneous rat mutant was identified that has markedly affected cone function, whereas rod-mediated function is largely spared. The presence of the normal number of cone outer segments indicates that the defect does not involve cone photoreceptor degeneration. This rat model provides a model of X-linked cone dysfunction, and may also be used to examine aspects of rod-mediated visual function in the rat. Further studies are needed to identify the gene that is involved.