Objective To analyze the protective effects of heat-shock response on the retinae of the rats after retinal ischemic reperfusion injury.Method Twenty Wistar rats (20 eyes) were divided into 4 groups: intracameral perfusion group (group P), intracameral perfusion after quercetin injection group (group P+Q), intracameral perfusion after heat shock group (group P+H), and in tracameral perfusion after quercetin injection and heat shock group (group P+Q+H ). According to the standard program established by International Society for Clinical Visual Electrophysiology, we recorded the results of the dark-adapted electroretinogram (D-ERG ),oscillatory potentials (OPs),and light-adapted ERG (L-ERG) of the rats with intraocular hypertension after induced by heat shock response. The expressions of HSP 70 of the rats in all groups were observed by Western blotting.Results The expression of HSP 70 of the rats in group P+H was the highest in all groups, but the expressions of HSP70 in group P+Q and P+Q+H were inhibited significantly. The amplitudes of a and b wave of ERG and O2 wave of OPs decreased, and the delitescence of them were delayed significantly in rats after intracameral perfusion. The amplitude of b wave of D-ERG and O2 wave of OPs in group P+H were higher than which in group P. Zero hour after perfusion, the amplitudes of all waves in group P+H increased significantly (Plt;0.05). Twenty-four hours after perfusion, the retinal functional resumption of the rats in group P+H was better than which in group P. In group P+Q and P+Q+H, the delitescences of all waves of ERG and O2 wave of OPs were the longest and the amplitudes were the lowest, and some waves even disappeared.Conclusions The heat-shock response may improve the recovery ability of the retinal cells after injury of ischemic reperfusion.(Chin J Ocul Fundus Dis，2003，19：117-120)
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 monitor the release of amino acids of the whole retina during and after experimental glaucoma by increasing the intraocular pressure （IOP）． Methods Experimental glaucoma was induced in one of the two eyes of rabbits by increasing IOP at 120 mm Hg for 45 min under infusion of saline in anterior chamber；then the pressure was released and the needle inserted into the anterior chamber was removed，this state was maintained for another 45 min．Every 15 min during the experiment 5 rabbits were killed and experimental eyes were enucleated．Aliquots（20 μl）of the retinal extracts（see below）were mixed with ophthaldialdehyde reagent and analysed for amino acid content by the HPLC method of Wangwei，using a 150 mm×4.6 mm,5 μm C18 column． Results A large increase in the release of glutamate，but not of the other three amino acids monitored，occurred during initial experimental ocular hypertension．It reached peak value of（111.73±17.46）10-5 mmol/g at 15 min of hypertension．15 min after release of intraocular pressure，again，immediately large and specific increase in the concentration of glutamate was reached to（102.96±51.91）10-5 mmol/g．In eyes subjected to paracentesis of anterior chamber，no difference was found between experimental eyes and controls. Conclusion These results suggest that glutamate is triggered by increasing the IOP，and it releases not only during the period of experimental ocular hypertension，but also afterwards. (Chin J Ocul Fundus Dis, 2002, 18: 146-148)
Objective To investigate the risk factors of the intraocular pressure (IOP) elevation after pars plana vitrectomy (PPV). Methods Eighty-eight patients (88 eyes) of postoperative ocular hypertension in a series of 339 patients who had undergone PPV with normal ocular pressure before operation were retrospectively studied. The ocular pressures in both preoperative and postoperative periods were detected by NCT examination, and the ocular hypertension was decided on the level of ≥25 mm Hg. The relationships of occurence of the time of onset and duration of persistence of postoperative ocular hypertension with the different kinds of primary diseases, the techniques of operation, and the condition whether or not the affected eyes had formerly accepted surgical intervention, were analyzed. Results The IOP elevation occures mostly within 1 to 2 weeks postoperatively (77 eyes, 87.5%). In 65 cases (65 eyes) IOP returned to normal in 1 week, and in another 14 cases (14 eyes) in 1 month after treatments. Six patients’ (6 eyes ) IOP was under 25 to 30 mm Hg with the medicine. With sustained elevation of IOP over 4 to 6 months, 3 cases (3 eyes ) lost or almost lost their vision finally. The probability of postoperative IOP elevation in the patients suffered from the retinal detachment with proliferative vitreoretinopathy (PVR) ≥grade C-2 was the highest in all the patients in our study (38.2%, P＜0.05). The patients who had intraocular surgery before were more likely to have IOP elevation than the ones without intraocular surgery (P＜0.05). Placement of a scleral buckle, use of expansile gases or silicone oil injection and scatter endophotocoagulation intraoperatively were related to the postvitrectomy IOP elevation (γ=0.829, P＜0.001). Conclusions The previous intraocular surgeries, certain primary eye diseases and combined ocular procedures are the risk factors of IOP elevation after PPV. (Chin J Ocul Fundus Dis, 2002, 18: 106-108)
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 analyse the changes of nitric oxide and nitric oxide synthase in rat retina under acute high ocular pressure and study the effect of nitric oxide in rat retinal damage under hypertension. Methods Sixty Wistar rats were divided randomly into five groups:Ocular hypertension 30 min,60 min,90 min and 12 h,24 h after reperfusion．Elevation of the ocular pressure in the anterior chamber of the rat eye ca used retina ischemic damage．The changes of retinal nitric oxide content were ob served indirectly by measuring NO2－/NO3－ content in retina.The distribution and changes of neuronal constitutive nitric oxide synthase (ncNOS)were studied by immunocytochemical localization of ncNOS. Results ncNOS positive neurons were distributed in the inner nuclear layer (INL),ganglion cell layer (GCL) and the inner plexiform layer of the normal and ischemic rat retina.During acute high IOP 30 min,60 min and 90 min,NO content decreased gradually and ncNOS immune activity weakens.During reperfusion,NO content increased remarkably (Plt;0.05) as compared with the groups of hypertension 90 min and decreased remarkably as compared with the normal rat retina.But ncNOS positive neurons continue to decrease compared with the groups of hypertension 90 min. Conclusion NO participates the rat retinal injury by acute elevated intraocular pressure, and nitric oxide synthetized by ncNOS may play an important role in protecting the retina from ischemic and post-ischemic injury.
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.
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.
Glaucoma is the leading cause of irreversible blindness worldwide, with its primary risk factor arising from elevated intraocular pressure (IOP) due to an imbalance between aqueous humor production and outflow. This study aims to establish quantitative correlations among IOP, iris mechanical properties, channel microstructures, and aqueous humor dynamics through three-dimensional modeling and finite element analysis, overcoming the limitations of conventional experimental techniques in studying aqueous flow within the trabecular meshwork (TM) outflow pathway. A three-dimensional fluid-structure interaction (FSI) model incorporating the layered TM structure, Schlemm’s canal (SC), iris, and other anterior segment tissues was developed based on human ocular anatomy. FSI simulations were performed to quantify the effects of IOP variations and iris Young’s modulus on tissue morphology and aqueous humor dynamics parameters. The computational results demonstrated that axial iris deformation showed significant correlations with IOP and iris Young’s modulus. Although elevated IOP exhibited minimal effects on hydrodynamic parameters in the anterior and posterior chambers, it markedly suppressed aqueous flow velocity in the TM region. Additionally, wall shear stress in SC and collector channels displayed high sensitivity to IOP variations. These findings reveal that the tissue mechanics-FSI mechanism modulates outflow resistance by regulating aqueous humor dynamics, offering valuable references for developing clinical therapies targeting IOP reduction in glaucoma management.