ObjectiveTo investigate the effect of erigeron breviscapus (EBHM) on ocular hypertension and the protective effect of retinal ganglion cells (RGCs) in rats by regulating mitogen activated protein kinase (MAPK) signaling pathway.MethodsSixty male Sprague-Dawley rats were divided into control group, model group, low-dose EBHM group (group A), medium-dose EBHM group (group B), and high-dose EBHM group (group C) by random number table method. There were 12 rats in the group, the left eye was used as the experimental eye. The rats of model group, group A, group B, and group C were infused with normal saline through the anterior chamber to construct an acute ocular hypertension model; the control group was given general anesthesia only. Then, 2-30 days after modeling, rats in the control group and model group were given 3 ml of normal saline once a day; rats in group A, group B, and group C were given 0.30, 0.45, and 0.60 g/100 g EBHM by intragastric administration, respectively, 1 time/d. The rat intraocular pressure was measured before modeling and 1, 14, and 30 days after modeling, and the proportion of high intraocular pressure model was measured. Thirty days after modeling, hematoxylin-eosin (HE) staining was used to observe the pathological changes of retinal tissue; immunofluorescence staining was used to detect the changes in the number of RGCs; real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect p38 in the retinas of rats in each group. The relative expression of MAPK and Caspase-3 mRNA; western blot was used to detect p38MAPK and phosphorylation in the retina of rats in each group relative expression of phosphorylate-p38MAPK (p-p38MAPK) and Caspase-3 protein. One-way analysis of variance was used for multi-sample comparison, and SNK-q test was used for comparison between two samples.ResultsOne day after modeling, none of the rats in the control group developed acute ocular hypertension, and the other groups were successfully modeled. Compared with the model group, the rates of acute ocular hypertension at 14 days after modeling in groups B and C were lower (χ2=98.701, P＜0.05), and the rates of acute ocular hypertension at 30 days after modeling in groups A, B, and C were 0. There was no statistically significant difference in the rates of acute ocular hypertension between 14 and 30 days after modeling in the A, B, and C groups (P＞0.05). The results of HE staining showed that the structure of the retina in the control group was complete, and the layers were clearly visible; the RGCs count was not abnormal, and the morphology was plump and round. The retina of rats in the model group became thinner; the number of RGCs was greatly reduced, the morphology was vacuolated, and the arrangement was sparse. The retina of rats in groups A, B, and C became thicker, and the number of RGCs increased, and the retina structure in group C was better restored. The results of immunofluorescence staining showed that the RGCs counts of rats in groups A, B, and C were higher than those in the model group, and the difference was statistically significant (F=297.514, P＜0.05); pairwise comparison between groups, group A was lower than that of group B and C Group (q=2.842, 5.263), group B was lower than group C (q=2.457), the difference was statistically significant (P＜0.05). The results of RT-qPCR and Western blot showed that compared with the model group, the relative expression of Caspase-3 mRNA (F=267.912) and protein (F=692.279) and the relative expression of p-p38MAPK protein in the retina of rats in groups A, B and C. The expression level (F=150.061) all decreased, and the difference was statistically significant (P＜0.05); pairwise comparisons between groups showed that Caspase-3 mRNA (q=6.977, 15.642) and protein (q=6.997, 15.642) relative expression levels and p-p38MAPK protein (q=12.443, 24.358) relative expression levels are lower than groups A and B, group B was lower than group A (q=11.678, 12.471, 10.204), the difference was statistical academic significance (P＜0.05).ConclusionsEBHM can significantly reduce intraocular pressure in rats with acute ocular hypertension, increase RGCs counts, and reduce retinal damage. Its regulatory mechanism may be related to the MAPK pathway.
Objective To observe the effects of minocycline to the viability and apoptosis of ratprime;s retinal neuron cells (RNC) under pressure, and to investigate the neuroprotective mechanisms of minocycline against the RNC damage. Methods Establish a model of ratprime;s RNs under pressure cultured in vitro, the protective effect of minocycline is observed by different methods, including observing the morphology of the cells, evaluating the cellsprime; viability by methyl thiazolyl tetrazolium (MTT) colorimetry assay, and detecting the cellular apoptosis with acridine orange/ethidium bromide (AO/EB) double staining by fluorescence microscopy. Immunocytochemistry was used to detect the expression of iNOS and caspase-3 in the cells. Results Obvious morphology changes of RNC were found in cells under pressure compared with the control; the viability of RNC decreased and cellular apoptosis was found in 53.93% cells. The cellular morphology improved in the cells treated by 20 mu;mol/L minocycline, the cellular viability significantly increased, and the cellular apoptosis was found in 17.29% cells. In addition, the expression of iNOS and caspase3 in the treated cells decreased compared with which in the pressured group. Conclusion Minocycline with a certain concentration can effectively inhibit pressureinduced damage and apoptosis of RNC of rats, and the inhibitory effect on expression of iNOS and capases-3 may be the underlying mechanism.
The occurrence of high intraocular pressure (IOP) after vitrectomy for diabetic retinopathy (DR) is related to many factors, including the type and stage of DR, macular detachment, surgical methods, and the type of ocular tamponade. Early high IOP occurred mainly due to laser photocoagulation, inflammatory response, improper ocular tamponade, residual viscoelastic agents and ciliary body dysfunction. In addition to the above reasons, early-middle stage high IOP is also related to tamponade gas expansion peak, encircling scleral buckle and hyphema. The major reason for middle-stage high IOP is hyphema and silicon oil in anterior chamber. The reasons for late-stage high IOP are glaucoma, silicone oil emulsification, long-term use of glucocorticoid, and iris incision closure. Most high IOP can be controlled by proper treatment such as stopping use of glucocorticoid, anti-glaucoma eye drops and surgeries. But there are still a small number of patients with unexplained refractory high IOP, the mechanism need to be further explored.
Objective To investigate the effect of proanthocyanidins (PC) on retina of rats with acute ocular hypertension. Methods The SpraqueDawley (SD) rats were randomly divided into the normal group, the model group and PC high or lowdosage group. The PC high or low dose group received 300mg/kg.d or 100mg/kg.d of PC in suspension solution for 5 days respectively. The normal group and the model group fed with distilled water for 5 days. Then acute ocular hypertension was induced in the model group and all PC groups, and after 48h of ocular hypertension the eyeballs were analyzed by electron microscope and UV spectrophotometer to measure the levels of superoxide dismutase(SOD), malonaldehyde (MDA), nitrogen monoxidum (NO), glutamic acid (Glu) and calcium ion(Ca2+). Results PC could raise the activity of SOD and reduced the levels of MDA,NO,Glu and Ca2+ in retina tissue. Electron microscope examination revealed that PC reduced retinal edema and ganglion cell apoptosis. PC also enhanced the SOD activity and suppressed the levels of MDA, NO, Glu and Ca2+. Conclusions PC can protect retina from acute ocular hypertension. The main mechanism might relate to anti-free radical oxidation, antagonizing calcium overloading, reducing toxicity of NO and Glu on the retina.
At present, there are few in vivo experimental studies on anterior chamber flow field, and the relevant technologies are not mature. This study explores the experimental method and key techniques of particle image velocimetry (PIV) for the in vivo measurement of anterior chamber flow field with slow flow velocity in the rabbit with acute intraocular hypertension. The experimental process can be divided into three parts: model construction of rabbit eye with acute intraocular hypertension, in vivo eyeball preparation, and PIV setup. The following key techniques were mainly investigated: the optimal injection strategy of fluorescent particles and the correction strategy for image acquisition errors caused by the effects of image refraction and respiration. The results showed that the best injection method was that 15 μL of fluorescent particles solution was slowly injected into the anterior chamber through the lower part of iris and then the rabbit was released and waited for 13 h. In this way particles were completely distributed in the anterior chamber with the help of the aqueous humor circulation, and then in vivo PIV experiment could be performed. The eyeball should be covered with a square flume filled with ultrasonic coupling gel for the sake of imaging during the experiment. The Maximal Information Coefficient algorithm could be applied to correct the measured results before post-processing calculation. The results indicated that feasible injection strategy of fluorescent particles and the correction strategy for image acquisition are critical to obtain nice experiment effects for the in vivo PIV measurement of anterior chamber flow field in the rabbit with acute intraocular hypertension.
In this paper,the changes of activities of enzymes relating toenergy metabolism in rabbit's retina during acute ocular hypertension were observed.The activities of succinate dehydrogenase and adenosine triphosphatase were foud to be reduced,while the activities of the lactatic dehydrognease and glucose-6-phosphatase increased.The results reveal the disturbance of metabolism of energy in retina undergone acute ocular hypertension,and suggest that this might be the underlying factors relating to the defects of the functions and structures of the retina. （Chin J Ocul Fundus Dis,1993,9:141-144）
Objective To evaluate the efficacy and safety of latanoprost versus travoprost for primary open-angle glaucoma (OAG) and ocular hypertension (OH). Methods All the randomized controlled trials (RCTs) about treating primary open-angle glaucoma and ocular hypertension with latanoprost and travoprost were collected by searching MEDLINE, EMbase, OVID and CNKI. The assessment of methodological quality and data extraction of the included studies were performed independently by two reviewers, and the meta-analysis was conducted with RevMan 5.0 software. Results A total of 13 RCTs involving 1 433 patients were included. The results of meta-analyses showed that, a) At the second week, travoprost showed greater intraocular pressure (IOP) lowering efficacy compared with latanoprost (WMD= –1.47, 95%CI –2.62 to –0.33). At the first month (WMD= –0.50, 95%CI –1.52 to 0.52) and the sixth month (WMD= –0.12, 95%CI –0.85 to 0.61), the difference of IOP reduction between latanoprost and travoprost group was not significant; and b) The latanoprost-treated group showed fewer reported conjunctival congestion than the travoprost-treated group (OR=0.47, 95%CI 0.35 to 0.63). The difference in adverse events of eye pain (OR=0.55, 95%CI 0.27 to 1.12) and iris or skin depigmentation (OR=1.25, 95%CI 0.53 to 2.92) between latanoprost and travoprost group was not significant. Conclusion Latanoprost and travoprost are comparable in lowering IOP for OAG and OH patients. Latanoprost shows greater ocular tolerability with lower incidence of side effects as conjunctival congestion. This conclusion is not powerful enough in proof due to the medium methodology quality of the included studies, so a large number of high-quality RCTs with large sample are needed for objectively, entirely and precisely evaluating the efficacy.
Objective To observe the clinical characteristics of steroid-induced ocular hypertension (SIOH) in patients with uveitis, and explore the relationship between its clinical phenotype and gene polymorphism. Methods A retrospective case-control study. From July 2019 to December 2020, 576 patients with uveitis who were treated with glucocorticoid eye drops in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 175 confirmed glucocorticoid responders (SRs) and 401 glucocorticoid non-responders (NRs). Seventy cases of SRs (age ≥18 years) using 1% prednisone acetate eye drops were selected as the experiment group and 64 cases of NRs were selected as the control group. The polymorphism of rs2523864 and rs3873352 of human leukocyte antigen complex group (HCG) 22 gene were detected by Sanger sequencing. To observe the clinical characteristics of SIOH after the use of glucocorticoid eye drops, and the correlation between rs2523864 and rs3873352 and the occurrence of SIOH. Differences among groups were compared with the Chi-square test or Fisher's exact test. The correlation between the occurrence of SIOH and the range of intraocular pressure increases after glucocorticoid use and the rs2523864 and rs3873352 loci were compared using the odds ratio (OR) and its 95% confidence interval (CI). Results SIOH occurred in 175 (30.4%, 175/576) of 576 patients. Among them, there were 96 males (54.9%, 96/175) and 79 females (45.1%, 79/175); the average age was 33.64±17.40 years. Steroid high responders (HRs) and steroid moderate responders (MRs) were 58 (33.1%, 58/175) and 117 (66.9%, 117/175) cases. The medication time for the increase in intraocular pressure in MRs that was 33 (19, 56) days, and in HRs that was 28 (14, 36) days, the difference of which was significant (Z=－1.999, P=0.046). No differences were found in daily doses of ocular hypertension induced by 1% prednisone acetate eye drops between MRs which was 4.24 (3.46, 4.66) drops/day and HRs that was 4.32 (3.84, 5.36) drops/day (Z=－1.676, P=0.094). The genotype and allele frequency distribution of the rs3873352 locus in the case group and HRs group were significantly different from those in the control group (P＜0.05). The intraocular pressure with rs3873352 GG genotype after the medication was higher than that with GC and CC genotype (Z=2.855, 2.628; P=0.013, 0.026), whereas there was no significant difference between different genotypes of rs2523864 (Z=3.580, P＞0.05). Genetic model analysis revealed the risk of SIOH in rs3873352 G allele carriers (GG+GC) was 2.048 times that of non-G allele carriers (OR=2.048, 95%CI: 1.027-4.081, P=0.041). The genotype and allele frequency of rs2523864 locus showed no significant difference between different group (P＞0.05). Conclusions After the use of glucocorticoid eye drops, HRs have an earlier increase in intraocular pressure than MRs. HCG22-rs3873352 gene polymorphism is related to the occurrence of SIOH, GG genotype increases the risk of SIOH, and G allele is a risk gene for SIOH.