ObjectiveTo analyze the protein expression changes in the retina of non-arteritic anterior ischemic optic neuropathy (NAION) in rats.MethodsThe rat NAION (rNAION) model was established by Rose Bengal and laser. Twenty Sprague-Dawley rats were randomly divided into 4 groups, the normal control group, the laser control group, the RB injection control group, and the rNAION model group, with 5 rats in each group. The right eye was used as the experimental eye. The retina was dissected at the third day after modeling. Enzyme digestion method was used for sample preparation and data collection was performed in a non-dependent collection mode. The data were quantitatively analyzed by SWATH quantitative mass spectrometry, searching for differential proteins and performing function and pathway analysis.ResultsCompared with the other three control groups, a total of 184 differential proteins were detected in the rNAION group (expression fold greater than 1.5 times and P＜0.05), including 99 up-regulated proteins and 85 down-regulated proteins. The expressions of glial fibrillary acidic protein, guanine nucleotide binding protein 4, laminin 1, 14-3-3γ protein YWHAG were increased. Whereas the expressions of Leucine-rich glioma-inactivated protein 1, secretory carrier-associated membrane protein 5, and Clathrin coat assembly protein AP180 were decreased. The differential proteins are mainly involved in biological processes such as nerve growth, energy metabolism, vesicle-mediated transport, the regulation of synaptic plasticity, apoptosis and inflammation. Pathway enrichment analysis showed that PI3K-Akt signaling pathway and complement and thrombin reaction pathway was related to the disease.ConclusionThe protein expressions of energy metabolism, nerve growth, synaptic vesicle transport and PI3K-Akt signaling pathway can regulate the neuronal regeneration and apoptosis in NAION.
Steady-state flsash visual evoked potentials (SFVEPs) of 30 Hz were recorded for 46 normal subjects (89 eyes )and 35 patients (51 eyes )with optic neuropathy. The visual acuities of 58.8%affected eyes were less than 0.1. The recorded waveforms were analyzed by discrete Foruier transform (DTF). The amplitudes and phases of fundamental response component and second harmonic were abstracted as characteristic values of the waveform.The total abnormal ratio was 80. 4%. The abnormal types showed the reduced amplitudes,reduced amplitude with phase change, the phases changes, and flat wave. The advantages of SFVEPs in clinical application were discussed. （Chin J Ocul Fundus Dis,1994,10:213-215）
Objective To observe the results of multifocal visual evoked potential (mfVEP) examination in patients with anterior ischemic optic neuropathy (AION) before and ater treatment, and to probe its clinical significance. Methods A total of 90 patients (90 eyes) with AION were examined by mfVEP; the secondorder reaction of mfVEP was analyzed.The reaction was divided into upper and lower hemi field of visual field, or 1/4 quadrant visual field (superior nasal, inferior nasal, superior temporal, and inferior temporal). The sum of waves of each response was analyzed and the results in various regions were compared.The features of wave configuration was compared between the AION eyes and the contralateral eye, and between the AION eyes before and after treatment.Results The amplitude and latency of P-wave of mfVEP was 0.198plusmn;0.033 and 100.197plusmn;7.354 respectively in AION eyes before treatment, and was 0.271plusmn;0.024 and 98.567plusmn;6.794 in the contralateral eyes; the difference was significant (t=16.556,18.330; Plt;0.01). The amplitude and latency of P-wave of mfVEP was 0.229plusmn;0.016 and 100.104plusmn;10.603 respectively in AION eyes after treatment, which differed much from that before the treatment (t=13.649, 8.858; Plt;0.01) and also from that of the contralateral eyes (t=13.649，8.858；P＜0.01). ConclusionsThe amplitude and latency of P-wave of mfVEP may accurately reflect the recovery of local optic nerve damage in AION eyes before and after treatment with good repeatability. AION can be used as a new method for AION diagnosis and detection of the prognosis.
Objectives To evaluate the risk factors of nonarteritic a nterior ischemic optic neuropathy（NAION）in a population of China and to provide theory basis for clinical decision. Methods Demographic features and clinical data of NAION were recorded. Cerebral infarction (CI) patients were also collected as control group. Systemic evaluations including whole blood chemical test, brain MRI, carotid artery ultrasound and fundus photography were perfor med in NAION and CI patients. The fundus photography and cup/disk ratio were als o acquired in a healthy controlgroup with matched age and gender. Statistical a nalysis was done by SPSS11.5 software. Results Thirtyeight N AION patients and 40 CI patients with intact data were included. Fundus photography and cup/disk ratio were acquired in 41 healthy individuals. No statistically significant difference regard to incidences of diabetes, male gender and lipid metabolic abnormalities was found between NAION and CI patients (Pgt;0.05). H ypertension, clinical and subclinical cerebral vascular disease and carotid ar tery stenosis were statistically more commonin CI patients than in NAION patien ts (Plt;0.01, 0.05). Cup/disk ratio was statistically significant smaller in NAION than in CI patients while no statistical difference (Pgt;0.05) was fo und between the CI group and healthy individuals. Conclusions NAION shared similar risk factors with cerebral infarction, but exposure of these risk factors was different between NAION and cerebral infarction. Hypertension , cerebral vascular disease and carotid artery stenosis were more common in cere bral infarction while diabetes, male gender and lipid metabolic abnormalities were similar. Small cup/disk ratio was an independent and the most important risk factor for NAION. (Chin J Ocul Fundus Dis,2008,24:86-89)
Objective It has been shown that pigment epitheliumderived factor (PEDF) is an effective anti-apoptosis agent on several kinds of cells of the central nervous system.This study aimed to evaluate the effect of PEDF on pressure induced retinal ischemia in a rat model. Methods Retinal ischemia was induced by increasing the intraocular pressure to 110 mm Hg for 45 minutes via an intracameral catheter.Ten microlit ers (0.1 mu;g/mu;l) PEDF was injected into the vitreous of 4 eyes of each group im mediately after reperfusion and 4 additional eyes received only normal saline as vehicle controls.The animals were euthanized at 2 or 7 days after reperfusion.T he effect of PEDF on retinal degeneration was assessed by measuring the thicknes s of the inner retinal layers (MTIRL) and counting the retinal ganglion cells (R GC) on plastic embedded retinal sections. Results The MTIRL and the RGC counting in eyes treated with intravitreal PEDF were significantly higher than those in vehicle controls (118.1plusmn;5.0) mu;m vs(94.9plusmn;3.0) mu;m (Plt;0.05);(6.0plusmn;1.0) cells/100 mu;m vs (4.5 plusmn;0.5) cells/100 mu;m (Plt;0.05) 7 days after reperfusion,respectively． Conclusion Intravitreal administration of PEDF can ameliorate an ischemiareperfusion retinal injury and may be useful to prevent neuronal degeneration in the inner retina. (Chin J Ocul Fundus Dis, 2001,17:138-140)
Objective To establish and evaluate a rat model of nonarteritic anterior ischemic optic neuropathy (NAION). Methods The rats were randomly divided into control group (n=13), sham laser group (n=11) and NAION group (n=23). The right eye was set as the experimental eye. NAION model was induced by directly illuminating the optic nerve (ON) of the right eye with 532 nm green laser, after intravenous infusion with the photosensitizing agent Rose Bengal. Sham laser treatment consisted of illuminating the ON region with 532 nm laser without Rose Bengal injection. Rats in control group underwent no intervention. The appearance of optic disc was observed with funduscope at 12 hours, 1, 3, 7, 28 days post-illumination. The histologic changes in the retina and ON of the NAION model were evaluated qualitatively with hematoxylin and eosin (HE) staining and transmission electron microscopy. The retrograde-labeled retinal ganglion cells (RGC) were counted on photographs taken from retinal flat mounts in a masked fashion. Results The optic disc in NAION eyes were swollen 3 days after photodynamic treatment. HE-stained longitudinal ON sections of NAION revealed vacuolar degeneration on day 3 after induction. Besides, ultrastructural study showed axonal edema and collapsed sheaths in the ischemic optic nerve at the same time point after modeling. ON edema resolved 7 days after induction. The final results revealed optic disc atrophy, extensive axonal loss, severe glial scar, and RGC death in large numbers 4 weeks after modeling. There were no aforementioned manifestations in control and sham laser group. The RGC density of the right eyes was statistically significantly lower in NAION group than that in control group and in sham laser group (t=?14.142, ?14.088; P=0.000, 0.000). The survival rate of RGC was statistically significantly lower in NAION group than in control group and in sham laser group (t=?17.048, ?16.667; P=0.000, 0.000). There was no difference of RGC density and survival rate of RGC between control and sham laser group (t=0.050, 0.348; P=0.961, 0.731). Conclusion A rat model of NAION was established successfully by photodynamic treatments with Rose Bengal, which induce optic nerve damage and RGC death.
Objective To observe the relationship between shallow optic cup，small disc and occurrence in patients with nonarteritic anterior ischemic optic neuropathy (NAION).Methods Ninetysix patients（96 diseased eyes）who accorded with the diagnosis criteria for NAION，with duration ge; three months and optic disc edema in paracmasis were selected. The fellow eyes of 96 NAION patients and 80 normal eyes were selected in our study. The horizontal and vertical disc and cup diameters，optic cup depth, and peripapillary retinal nerve fiber layer (RNFL) thickness were measured by quot;crossquot; and quot;ringquot; scan of optical coherence tomography (OCT，Humphrey 2000，German Carl Zeiss Company) inspection system. The cup depth were classified four grades by cup shape according to OCT images：GradeⅠ，bottom of optic cup above the anterior plane of peripapillary neuroepithelial layer（PNL）；GradeⅡ，bottom of optic cup above the plane of PNL；Grade Ⅲ，bottom of optic cup between the plane of PNL and choroidal pigment epithelium；Grade Ⅳ，bottom of optic cup under the plane of choroidal pigment epithelium connection. The grades of optic cup and value in three groups were statistically analyzed. The follow up ranged from six months to three years.Results The disc diameter in horizontal scanning of diseased eyes，fellow eyes and normal eyes were (1.29plusmn;0.19), (1.32plusmn;0.17), (1.40plusmn;0.15) mm，and diameters in vertical scanning were (1.52plusmn;0.14), (1.49plusmn;0.17), (1.60plusmn;0.22) mm, respectively. Compared the diseased eyes and fellow eyes with normal eyes，the difference were statistically significant in horizontal scanning (t=4.291,3.315; P＜0.05) and in vertical scanning (t=2.812, 3.654; P＜0.05). Compared the diseased eyes with fellow eyes，the difference of average diameter were not statistically significant in horizontal and vertical scanning (t=1.153,1.335; P＞0.05). Of the diseased eyes，GradeⅠoptic cup in 36 eyes（37.50），Grade Ⅱ-Ⅲoptic cup in 52 eyes（54.17%），Grade Ⅳoptic cup in eight eyes（8.33%），and GradeⅠ-Ⅲ optic cup in 88 eyes（91.67%）were found. Of the fellow eyes，GradeⅠoptic cup in 18 eyes（18.75%），Grade Ⅱ-Ⅲoptic cup in 69 eyes（71.88%），Grade Ⅳoptic cup in nine eyes（9.34%），and GradeⅠ-Ⅲ optic cup in 87 eyes（9066%）were found. Compared the average RNFL thickness of diseased eyes with the fellow eyes and normal eyes，the differences were statistically significant in temporal, upper, nasal, lower quadrant(t=12.862，10.147，15.046，8.180，12.859，9.562，12.174，8.632；P＜0.001). Compared the average RNFL thickness of the fellow eyes and normal eyes，the differences were not statistically significant in all quadrants（t=1.040，1.576，1.062，1.192；P＞0.05）. During the followup，eight eyes with recurrence which optic cup were GradeⅠand Ⅱin diseased eyes；44 eyes（45.8%）occurred NAION. Correlation analysis showed that there was negative correlation between incidence of fellow eye and optic cup depth(t=-0.757, P=0.000). Conclusion Optic cup and disk in NAION patients are smaller than that in the normal，the anatomical characteristics of shallow cup and small disc was one of the NAION pathogenesis.
ObjectiveTo investigate the association of high density lipoprotein cholesterol (HDL-C) and cholesterol ester transfer protein (CETP) TaqIB mutation with non-arteritic anterior ischemic optic neuropathy (NA-AION) in the Shaanxi Han ethnic population. MethodsThe study cohort consisted of 45 individuals that had been diagnosed with NA-AION and 45 healthy controls (matched for age, gender). None of the cases or controls had a history of diabetes, serious cardio-cerebral vascular diseases, liver and kidney dysfunction that might influence plasma lipid levels. Plasma HDL-C was detected by enzyme-linked immunosorbent one-step, through the Toshiba TBA-40FR automatic biochemical analyzer. CETP TaqIB gene polymorphism was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques for analysis. B2B2 genotype was only a fluorescence band with 535 bp; B1B1 genotype was 2 fluorescence bands with 361, 174 bp; B1B2 genotype was 3 fluorescence bands with 535, 361, 174 bp. The relative risk of genotype, HDL-C and disease occurrence was analyzed by logistics regression analysis. ResultsThere have no significant difference between NA-AION patients and controls about plasma total cholesterol level and triglyceride level (t=1.907, 1.877; P > 0.05). The plasma HDL-C levels were significantly lower in NA-AION patients than in controls (t=2.367, P=0.022). Compared with controls, the prevalence of B1B1 genotype and B1 allele was higher (χ2=17.289, P=0.001), the prevalence of B2 allele (χ2=15.648, P=0.000) was lower in NA-AION patients. The lower concentration of HDL-C was risk factor of NA-AION (odds ratio=6.143, 95% confidence interval 1.262-29.895, χ2=27.676;P=0.013). The proportion of B1B1 genotype was significantly higher in NA-AION patients than in controls (odds ratio=2.24, 95% confidence interval 2.427-36.323, χ2=10.526; P=0.001). ConclusionsThe low plasma HDL-C is independent risk factor for NA-AION and is associated with the development of NA-AION in the Shaanxi Han ethnic population. CETP TaqIB mutation is associated with low plasma HDL-C in NA-AION in the Shaanxi Han ethnic population.
Critical flicker fusion frequency (CFF) is a dynamic visual function test that measures the minimum frequency at which a flicker source is perceived by the visual system as continuous light. The measurement method is convenient, the inspection time is short, and it can be effectively evaluated in the case of refractive interstitial opacity. Although CFF has many advantages, its application in the field of ophthalmology has not received sufficient attention. The pathway of CFF involves the pathway from the retina to the lateral geniculate body to the primary visual cortex, where the macrocellular pathway is sensitive to temporal resolution and responsible for transmitting rapidly changing information. Its measurements typically use red, green, or yellow light as a flashing light source to detect the functional integrity of the macular region. As a subjective test, the results of CFF can be affected by a variety of factors, such as drug use, fatigue, and luminous intensity. In order to improve the repeatability of the measurement, it is necessary to follow standardized measurement steps. CFF has important application value in the diagnosis of optic nerve diseases. It can assist in diagnosing the presence of optic neuropathy, evaluating the conduction function of the optic nerve, and monitoring the progression of the disease and the effect of treatment. As a convenient and efficient visual function evaluation tool, CFF has great potential in the diagnosis of optic nerve diseases and visual function monitoring. In view of its application prospects in the field of ophthalmology, this study calls for more attention and support from ophthalmologists, and carry out related basic and clinical research to further explore the application value of CFF in different disease conditions.
ObjectiveTo investigate the neuroprotective effect of Benztropine on retinal ganglion cells (RGCs) death and optic nerve injury in rats model of non-arteritis anterior ischemic optic neuropathy (rNAION).MethodsA total of 25 Sprague-Dawley rats were randomly divided into Benztropine treatment group (n=13) and PBS control group (n=12). The right eye was set as the experimental eye. rNAION model was established by using rose Bengal combined with laser photodynamic method. The rats in the Benztropine treatment group were received intraperitoneal injection with Benztropine 10 mg/kg (0.2 ml) daily for 3 weeks, while the rats in the PBS control group were received intraperitoneal injection with an equal volume of PBS. At 1, 3 and 7 days after modeling, the retinal and optic disc conditions of the rats were observed by direct ophthalmoscopy. Retrograde labeling, fluorescence microscopy and transmission electron microscopy were used to observe the survival of RGCs and the damage of the optic nerve myelin and axon at 4 weeks after modeling. The RGCs density and survival rate of the two groups were compared by One-Way Anova.ResultsAt 1 and 3 days after modeling, the optic disc edema was observed in the rats of rNAION model group. At 7 days after modeling, the optic disc edema decreased and the boundary was blurred compared with 3 days after modeling.After 4 weeks, the RGCs density in the PBS group was 308±194/mm2 and the survival rate was 13.7%. The density of RGCs in the Benztropine group was 1173+868/mm2 and the survival rate was 47.6%. The differences of RGCs density and survival rate were significant between the two groups (F=7.552, 8.184; P=0.015, 0.012). Myelin disintegration, axon degeneration, onion-like body and gliosis were observed in the optic nerve sections of rNIAON in the PBS group, while the damage of axon and myelin structure in the Benztropine group was significantly less than that in the PBS group.ConclusionsBenztropine group showed higher RGC survival rate, less damage of axon and myelin structure on rNAION model. This study explored the potential neuroprotective effect of Benztropine.