NMI,POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure:a clue for early diagnostic biomarker candidates

AIM:To understand the molecular connectivity between the intraocular pressure(IOP)and glaucoma which will provide possible clues for biomarker candidates.METHODS:The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma.An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes(DEGs)in both conditions.To the selected DEGs,the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma.For the clusters,the connectivity of IOP DEGs was determined.Further,enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.RESULTS:The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs(277 glaucoma and 131 IOP genes)were discovered from two GEO datasets.The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges.Using ClusterONE,the network was dissected to have 12 clusters.Among them,three clusters were linked with three IOP DEGs[N-Myc and STAT Interactor(NMI),POLR3G(RNA Polymerase Ⅲ Subunit G),and APAF1-interacting protein(APIP)].In the clusters,ontology analysis revealed that RNA processing and transport,p53 class mediators resulting in cell cycle arrest,cellular response to cytokine stimulus,regulation of phosphorylation,regulation of type Ⅰ interferon production,DNA deamination,and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma.Finally,NMI,POLR3G,and APIP may have roles that were noticed altered in glaucoma and IOP conditions.CONCLUSION:Our findings could help to discover new potential biomarkers,elucidate the underlying pathophysiology,and identify new therapeutic targets for glaucoma.

Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain unknown.Rat models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular pressure.Our results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and fibroblasts.The single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular pressure.We extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct expression.We found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of inflammation.This study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular pressure.These data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

The modulating of Qingguang’anⅡFormula on gut microbiota in mice with chronic high intraocular pressure by 16S rDNA sequencing

Objective To investigate the effects of Qingguang'anⅡFormula(QGAⅡ)on the gut micro-biota of mice with chronic high intraocular pressure(IOP)model,and explore its key micro-biota for protecting the optic nerve.Methods A total of 10 specific pathogen free(SPF)grade female DBA/2J mice were random-ly divided into model group and QGAⅡgroup(n=5 for each group),while additional 5 SPF-grade female C57BL/6J mice were assigned to control group.Mice presented spontaneous high IOP and showed elevated approximately at the age of seven months.The high IOP was maintained until week 38,when gavage was initiated.Mice in control group underwent the same intragastric treatment,while those in QGAⅡgroup were gavaged with QGAⅡ(9.67 g/kg),once a day for four weeks.Retinal morphology was examined using hematoxylin and eosin(HE)staining,with the number of retinal ganglion cells(RGCs)counted.The expression level of Brn3a protein,a specific marker for RGCs,was detected by immunofluorescence,with the mean optical density(OD)measured for quantitative analysis.In addition,16S rDNA se-quencing was leveraged to analyze changes in the diversity of gut microbiota,including theirα-diversity(Chao1,Shannon,Pielou’s evenness,and observed species index)andβ-diversity.Venn diagrams and linear discriminant analysis effect size(LEfSe)analysis was employed to investigate the number of amplicon sequence variants(ASVs),the abundance of differential gut microbiota species,and the classification of species at both the phylum and genus levels within the three groups of mice.Results HE staining revealed that compared with control group,model group showed signif-icant reduction in the number of RGCs(P<0.01),with intracellular vacuolar degeneration and nuclear pyknosis.After QGAⅡtreatment,the number of RGCs was significantly in-creased compared with model group(P<0.01),with notable improvements in intracellular vacuolar degeneration.Immunofluorescence analysis showed that the mean OD of Brn3a protein was significantly decreased in model group compared with control group(P<0.01),while QGAⅡtreatment significantly elevated its expression level(P<0.01).Analysis ofα-diversity showed that after QGAⅡintervention,the Chao1,Shannon,and Pielou’s evenness indices were significantly increased(P<0.01),and the observed species index was elevated(P<0.05).β-Diversity analysis demonstrated distinct clustering among the three groups,indicating relatively low similarity in bacterial community structures.ASV clustering identi-fied a total of 14061 ASVs across all groups,with 9514 ASVs shared between model and QGAⅡgroups.At the phylum level,the abundance of Bacteroidetes was significantly decreased in model group compared with control group(P<0.01),while Firmicutes and the Firmicutes/Bacteroidetes(F/B)ratio were significantly increased(P<0.01).QGAⅡtreatment significantly reduced both Firmicutes abundance and the F/B ratio(P<0.01).At the genus level,Lactobacillus was dominant across all groups,with its abundance significantly in-creased in model group(P<0.01)and subsequently decreased following QGAⅡintervention(P<0.05).Conclusion QGAⅡrestructured the gut microbiota of DBA/2J mice with chronic high IOP,bringing changes in their diversity and abundance of components.Firmicutes,Bacteroidetes,Lactobacillus,along with their associated microorganisms,are likely critical components of the gut microbiota that contribute to the optic neuroprotective effects of QGAⅡon chronic high IOP mice.

Protective limb remote ischemic post-conditioning against high-intraocular-pressure-induced retinal injury in mice

AIM: To determine whether limb remote ischemic postconditioning(LRIC) protects against high-intraocularpressure(IOP)-induced retinal injur y, and to identify underlying molecular mechanisms. METHODS: In mice, IOP was increased to 110 mm Hg for 50 min and LRIC applied to the unilateral leg for three occlusion cycles(5 min/release). Three animal groups(control, high IOP, and high IOP+LRIC) were arranged in this study. Plasma was collected from LRIC treated mice. Retinal histology, oxidative stress were determined by histological section staining and chemical kit. C/EBP homologous protein(CHOP), and Iba-1 parameters were evaluated by immunofluorescent staining and Western blot. RESULTS: The data showed that LRIC treatment alleviated the retinal histological disorganization and ganglion cell loss induced by high IOP. The CHOP, Iba-1 expression and oxidative stress marker also were inhibited by LRIC treatment. To further explore underlying mechanisms, plasma from LRIC treated animals was intravenously transfused into high-IOP animals. The results showed plasma injection decreased caspase 9 expression and DHE staining signals compared with that in high IOP retinas. CONCLUSION: These data suggest that LRIC treatments exert retinal protective effects against high-IOP injury.Endogenous humoral factors release into the circulation by LRIC may contribute to homeostatic protection by reducing monocyte infiltration and/or microglia activation.

Dynamic changes of inducible nitric oxide synthase expression in rat's retina and its role on blood-retinal barrier injury after acute high intraocular pressure

AIM: To clarify the role of inducible nitric oxide synthase(i NOS) in blood-retinal barrier(BRB) injury after acute high intraocular pressure(IOP) in rats.METHODS: Forty-two Sprague-Dawley(SD) rats were randomized into 7 groups [control(Cont), 3, 6, 12, 24, 48, and 72 h, n=6]. Except Cont group, other groups’ retina tissue was obtained at corresponding time points after a model of acute high IOP have been established in rats. The expression of i NOS and tight junction protein zonula occludens(ZO)-1 was detected by Western blotting. Evans blue(EB;3%) was injected into the great saphenous vein to detect the leakage of EB by spectrophotometer. Nine rats were divided into Cont, 6 h, 12 h groups, the expression of i NOS was localized by immunofluorescence. In order to verify the role of i NOS in the damage to BRB, thirty-six rats were randomly divided into 4 groups [Cont, Cont+inhibitor(Inh), 6 h and 6 h+Inh, n=9]. After treatment with the i NOSspecific inhibitor 1400 W, the expression of i NOS and ZO-1 and the leakage of BRB were detected again.RESULTS: The immunofluorescence results showed that the expression of i NOS was observed in the Cont group and 6 h group, but not in the 12 h group. i NOS was mainly expressed in the retinal nerve fiber layer, ganglion cell layer and inner nuclear layer and that it did not colocalize with the retinal ganglion cell marker Neu N but was co-expressed with the vascular endothelial cell marker CD31. Western blotting showed that in the early period(3 h, 6 h) after acute high IOP, the expression of i NOS was upregulated, then the down-regulation of i NOS were tested in the follow-up timing spots. ZO-1 expression showed a continuous downregulation after 6 h. The quantitative results for EB showed that the amount of EB leakage began to increase at 3 h after acute high IOP. At 6 h, the leakage of EB was lower, but at 12 h, the leakage of EB was highest, after which it gradually recovered but remained higher than that in the Cont group. The expression of i NOS was down-regulated after 1400 W treatment. ZO-1 expression was not significantly changed in the Cont+Inh group and the 6 h group, and significantly down-regulated in the 6 h+Inh group, and the leakage of EB was significantly increased after 1400 W treatment.CONCLUSION: These results suggest that the upregulation of i NOS expression in the early stage after acute high IOP may have a protective effect on BRB injury.

Effect of Qingguang'anⅡon expressions of OX42 protein and IL-1βmRNA of retinal microglia cells of rats with chronic high intraocular pressure

The study investigated the effects of Qingguang＇an Ⅱ（a Chinese medicinal preparation） on expressions of OX42 protein and interleukin-1β（IL-1β） mRNA of retinal microglia cells of rats with chronic high intraocular pressure（IOP）. SD rats were randomly divided into 6 groups, that were： A： blank group; B： model group; C： Qingguang＇an Ⅱ low dose group; D： Qingguang＇an Ⅱ medium dose group; E： Qingguang＇an Ⅱ high dose group; F： Yimaikang disket（a Chinese medicinal preparation） group. Experimental rats in B, C, D, E, F groups were established the model of chronic high IOP by cauterizing of superficial scleral vein. Tissues of eyes were obtained after intragastric administration for 2 and 4 wk. At the time-point of 2 wk, OX42 protein and IL-1β mRNA in group B were statistically expressed in higher level comparing with other groups（P〈0.05）. Moreover, at the time-point of 4 wk, OX42 protein and IL-1β mRNA in groups C, D and E were statistically expressed in lower level comparing with group F（P〈0.05）. Besides, OX42 protein and IL-1β mRNA in groups C and D were statistically expressed in higher level comparing with group E（P〈0.05）. OX42 protein and IL-1β mRNA in groups C and D were expressed in similar level（P〉0.05）. The study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang＇an Ⅱ at the time-point of 4 wk was the better choice.

Bioinformatics analysis of potential essential genes that response to the high intraocular pressure on astrocyte due to glaucoma

AIM: To study the gene expression response and predict the network in cell due to pressure effects on optic nerve injury of glaucoma.METHODS: We used glaucoma related microarray data in public database [Gene Expression Omnibus(GEO)] to explore the potential gene expression changes as well as correspondent biological process alterations due to increased pressure in astrocytes during glaucoma development.RESULTS: A total of six genes were identified to be related with pressure increasing. Through the annotation and network analysis, we found these genes might be involved in cell morphological remodeling, angiogenesis,mismatch repair.CONCLUSION: Increasing pressure in glaucoma on astrocytes might cause gene expression alterations,which might induce some cellular responses changes.

TrkB and p-trkB expression in brain-derived neurotrophic factor-pretreated rat retina following acute high intraocular pressure

BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kinase receptor B （trkB） expression and effects of exogenous BDNF on trkB activation in a rat model of acute high intraocular pressure （HtOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Anatomy and Neurobiology, Xiangya Medical School, Central South University from January 2004 to August 2006. MATERIALS： Rabbit anti-BDNF and anti-trkB.FL（full-length） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA; rabbit anti-p-trkB polyclonal antibodies were purchased from Cellsignal, USA. METHODS： A total of 48 healthy, adult, Sprague Dawiey rats were randomly assigned to acute HIOP （without BDNF pre-treatment） and BDNF pre-treated groups, with 24 animals in each group. In the BDNF pre-treated group, the left eyes were intravitreally injected with 3 pg/kg BDNF 2 days prior to HIOP. Rats in the acute HIOP group were not pre-treated with BDNE HIOP models were established by increased intraocular pressure in the left eyes until the b-wave of flash electroretinogragh disappeared and pressure was maintained for 60 minutes. The right eyes of all rats were not treated and served as the normal controls. MAIN OUTCOME MEASURES： Retinal structure and cell numbers in the ganglion cell layer （GCL） were detected by Nissl staining; expression of trkB and phosphorylated trkB in the rat retina were determined by immunohistochemistry. RESULTS： A greater number of GCL neurons were observed in the pre-treated group compared to the acute HIOP group （P 〈 0.05）. TrkB expression was significantly increased following HIOP at days 1 and 3 （P 〈 0.05）, but expression varied between retinal areas. Although trkB expression decreased at 7 days, phosphorylated trkB dramatically decreased with increasing time （P 〈 0.05）. TrkB expression in BDNF pre-treated rats was similar to the acute HIOP group at early injury time points. Nevertheless, trkB expression was significantly decreased compared to the acute HIOP group at 7 days （P 〈 0.05）, and phosphorylated trkB expression was significantly greater compared to the acute HIOP group at each time point （P〈 0.05）. CONCLUSION： TrkB expression displayed temporal and spatial changes in the rat retina following acute HIOP, and trkB up-regulation suggested that more BDNF was required for treating the injured retina. Exogenous BDNF partially ameliorated decreased expression of phosphorylated trkB and provided protection to the injured retina, to a certain degree, following HIOP.

Does high intraocular pressure exclude an open globe injury?

Dear Sir,Ocular trauma is a topic of unresolved controversies and there are continuous controversial and debatable diagnostic and management strategies for open-globe injuries[1].Amongst many types of ocular trauma,the open globe injury is the most serious due to its very poor visual prognosis and young population of patients are mostly affected[2].The treatment outcome may be improved by prompt diagnosis,and immediate surgical repair performed to high standard[3].Amongst the other clinical signs the intraocular pressure(IOP)is found to be particularly reduced and conventionally this is considered as a very reliable indicator of occult globe

Vascular endothelial growth factor-165b protects the blood-retinal barrier from damage after acute high intraocular pressure in rats

AIM:To elucidate the role of vascular endothelial growth factor-165b(VEGF-165b)in blood-retinal barrier(BRB)injury in the rat acute glaucoma model.METHODS:In this study,the rat acute high intraocular pressure(HIOP)model was established before and after intravitreous injection of anti-VEGF-165b antibody.The expression of VEGF-165b and zonula occludens-1(ZO-1)in rat retina was detected by double immunofluorescence staining and Western blotting,and the breakdown of BRB was detected by Evans blue(EB)dye.RESULTS:The intact retina of rats expressed VEGF-165b and ZO-1 protein,which were mainly located in the retinal ganglion cell layer and the inner nuclear layer and were both co-expressed with vascular endothelial cell markers CD31.After acute HIOP,the expression of VEGF-165b was up-regulated;the expression of ZO-1 was down-regulated at 12h and then recovered at 3d;EB leakage increased,peaking at 12h.After intravitreous injection of anti-VEGF-165b antibody,the expression of VEGF-165b protein was no significantly changed;and the down-regulation of the expression of ZO-1 was more obvious;EB leakage became more serious,peaking at 3d.EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina.CONCLUSION:The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1.The differential destruction of BRB after acute HIOP may be related to the selective loss of retinal ganglion cells.

Influence of transient intraocular pressure elevation during laser in situ keratomileusis on rabbit retina thickness

AIMTo utilize tissue micro measurement to study the effect of transient high intraocular pressure (IOP) induced by different durations of suction during laser in situ keratomileusis (LASIK) on rabbit retina thickness.METHODSSixty healthy New Zealand white rabbits were randomly divided into a control group, and 3 negative-pressure suction groups (20s group, 45s group, and 3min group) and each group was comprised of 15 rabbits (30 eyes); the latter 3 groups were the transient high IOP models. The retinal tissue around the papilledema was separated. Hematoxylin and eosin (HE) staining was carried out to generate slices for light microscopy. The changes in the retina thickness values of each layer were measured for all animals in each group at different postoperative recovery periods and compared with the values recorded for the animals in the control group. The thickness of the retinal tissue showed a normal distribution. The ANOVA was performed by using SPSS13.0 statistic software.RESULTSIn the comparison between the 20s and 45s negative-pressure suction groups and the control group, no significant differences were observed, except at 14d. Significant difference was observed between the 3min negative-pressure suction group and the control group, and the retina thickness value of each layer reached a peak at 14d after repair.CONCLUSIONConventional negative suction during LASIK may not lead to significant changes in retinal tissue thickness; however, if the suction duration is increased to 3min, it will cause significant changes in retinal tissue thickness.

Longitudinal observation of intraocular pressure variations with acute altitude changes

BACKGROUND Higher intraocular pressure(IOP)is a major risk factor for developing glaucoma,and the leading cause of irreversible blindness worldwide.High altitude(HA)may be involved in IOP,but the reported results were conflicting.Ascent to HA directly by plane from low altitude regions is an acute,effortless exposure.However,the effects of such exposure to different altitudes on IOP have rarely been reported.AIM To investigate changes in IOP after rapid effortless exposure to HA in stages and compare it with systemic parameters.METHODS Fifty-eight healthy subjects(116 eyes)were divided into three groups:17 lowaltitude(LA)residents[44 m above sea level(ASL)],22 HA residents(2261 m ASL)and 19 very HA(VHA)residents(3750 m ASL).The LA group flew to HA first.Three days later,they flew with the HA group to VHA where both groups stayed for 2 d.Then,the LA group flew back to HA and stayed for 1 d before flying back to 44 m.IOP,oxygen saturation(SpO2)and pulse rate were measured.The linear mixed model was used to compare repeated measurements.RESULTS IOP in the LA group significantly decreased from 18.41±2.40 mmHg at 44 m to 13.60±3.68 mmHg at 2261 m ASL(P<0.001),and then to 11.85±2.48 mmHg at 3750 m ASL(P=0.036 compared to IOP at 2261 m ASL)and partially recovered to 13.47±2.57 mmHg upon return to 44 m.IOP in the LA group at HA and VHA was comparable to that in the local residents(12.2±2.4 mmHg for HA,11.5±1.8 mmHg for VHA).IOP was positively associated with SpO2 while negatively associated with pulse rate.CONCLUSION IOP in the LA group gradually reduced as altitude elevated in stages and became comparable to IOP in local residents.Hypoxia may be associated with IOP,which deserves further study.

Efficacy of ripasudil in reducing intraocular pressure and medication score for ocular hypertension with inflammation and corticosteroid

·AIM:To investigate the efficacy of ripasudil,a Rho kinase inhibitor,in reducing intraocular pressure(IOP)and medication scores of anti-glaucoma drugs in patients with ocular hypertension with inflammation and corticosteroid.·METHODS:The study included 11 patients diagnosed with ocular hypertension with inflammation and corticosteroid,all of whom were prescribed ripasudil eye drops and followed up for at least 2y after the initiation of treatment.IOP was measured using a non-contact tonometer before enrollment and at each follow-up visit.The medication score of glaucoma eye drops was calculated for each patient.·RESULTS:The mean IOP(26.4±2.9 mm Hg before treatment)significantly decreased after ripasudil therapy(13.7±3.3 mm Hg at 3mo)and remained stable in the low-teens during the 2-year follow-up period(P<0.0001).A significant decrease in the medication score was observed at 12mo or later after the initiation of ripasudil therapy(P<0.05).Both baseline medication scores and glaucomatous optic disc change rates were significantly higher in the five eyes that required glaucoma surgery during the 2-year observation period than the 10 eyes that did not require surgery.·CONCLUSION:Our results demonstrate the efficacy of ripasudil,in reducing IOP and the medication score over a 2-year treatment period in patients with ocular hypertension with inflammation and corticosteroid.Our findings also suggest that ripasudil could reduce the IOP in uveitic glaucoma patients with both lower baseline medication score and lower glaucomatous optic disc change rate.

Effects of chronic elevated intraocular pressure on parameters of optical coherence tomography in rhesus monkeys

AIM: To determine the progression of parameters from optical coherence tomography(OCT) in chronic elevated intraocular pressure(IOP) monkeys.METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer(RNFL) thickness, and parameters from optic nerve head(ONH) analysis were collected before and after laser treatments biweekly for up to 28 wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model.RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37 wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2 wk after elevated IOP induction(P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk.CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.

综合护理用于持续性高眼压状态下原发性闭角型青光眼效果分析

目的探讨综合护理用于持续性高眼压状态下原发性闭角型青光眼的效果。方法选取医院2021年2月至2023年2月收治的持续性高眼压状态下原发性闭角型青光眼患者64例,按盲摸双色球法均分为对照组和观察组,各32例。对照组患者给予一般护理,观察组患者加用综合护理。结果术后,观察组患者眼压及前房深度均显著低于对照组(P<0.05);观察组患者住院时间显著短于对照组(P<0.05);观察组并发症发生显著低于对照组(P<0.05);观察组患者护理满意程度显著高于对照组(P<0.05)。结论综合护理可显著改善持续性高眼压状态下原发性闭角型青光眼患者的相关指标、并发症发生情况及护理满意程度。

高度近视与原发性开角型青光眼临床特征的研究进展

随着人们生活方式的显著改变,全球近视患病率日益上升,引发了临床医生的密切关注。近视易合并其他严重的眼科疾病,尤其是高度近视(HM)患者,常合并原发性开角型青光眼(POAG),其发病率远远高于屈光状态正常的人群。当高度近视与原发性开角型青光眼并存时,病情变得尤其复杂。近年我们在临床工作中集中关注患者的眼底改变特征。从高度近视人群中早期发现原发性开角型青光眼患者,这是对两种疾病深入了解并进行有效防治的关键。文章通过回顾分析近年文献,从流行病学、发病机制及临床特征方面对高度近视与原发性开角型青光眼的关系及研究进展进行综述,以期为疾病早期发现、早期诊断、早期治疗提供帮助。

高眼压作用下大鼠小梁网组织弹性模量的变化

目的探究高眼压持续作用不同时间下大鼠小梁网组织弹性模量的变化情况,为深入研究小梁网组织的力学特性与房水外流阻力之间的关系提供基础。方法选取18只SD雄性大鼠,体重控制在260~300 g。右眼通过烙闭上巩膜静脉建立高眼压实验组模型,左眼不做任何处理作为对照组,并分别在2周、3周、4周取下眼球后制作小梁网组织横截面冰冻切片,利用原子力显微镜对小梁网区域进行纳米压痕实验,使用Sneddon接触模型对压痕曲线进行拟合,得到高眼压作用持续不同时间下小梁网弹性模量的变化情况。结果实验组与对照组眼压差异具有显著性,说明成功建立了高眼压动物模型。2周、3周、4周实验组的小梁网弹性模量分别为(20.55±5.68)kPa、(23.98±4.42)kPa、(28.56±5.94)kPa,明显大于各自的对照组,且不同时间点3个实验组的小梁网组织弹性模量也存在统计学上的差异。结论随着高眼压的持续作用,小梁网组织弹性模量明显增大,且与作用时间呈正相关。这一发现一定程度上考虑了高眼压对小梁网力学性质的影响,为深入了解高眼压对眼球生理机制的影响提供了重要线索,所得结果对房水外流阻力增大机制的研究具有参考意义。

Effect of high myopia on 24-hour intraocular pressure in patients with primary open-angle glaucoma

Background As intraocular pressure （lOP） and lOP fluctuation are known risk factors for glaucoma, it is important to understand the effects of high myopia on these ocular parameters. The aim of this study was to investigate if primary open-angle glaucoma （POAG） patients with high myopia exhibit higher lOP and greater lOP fluctuations at resting conditions over 24 hours. Methods We designed a prospective control clinical study. Eighty-two eyes of 82 high-tension Chinese POAG patients only on prostaglandin analogue locally were divided into 3 groups according to various myopic grades （〈-6.0 D, n=27 and between -0.76 and -5.99 D, n=33） or without myopia （-0.75 to 0.75 D, n=22）. Single time lOP at 10 am, mean corrected 24-hour lOP, mean corrected night lOP, 24-hour lOP fluctuation and lOPs of 10 am, 2 pm, 6 pm, 10 pm, 2 am, 6 am and 8 am were measured. Results The lOP was higher in POAG patients with high myopia over those POAG alone in three ways： the elevated lOP value was 0.65 mmHg measured in single time lOP at 10 am, 0.84 mmHg in mean corrected 24-hour lOP, 0.97 mmHg in mean corrected night lOP. The 24-hour lOP fluctuation was lower in the two myopia groups than in non-myopia group. Further, using repeated measurement analysis of variance, there was no statistical significance among groups regarding the lOPs at the seven time points （P=0.77） and there was no interaction between groups and time points （P=0.71）, but the difference of lOPs at the seven time points in same group was statistically significant （P=0.01）. Conclusion High-tension POAG patients with high myopia, even on pharmacological glaucoma therapy, still have hinhe.r IC）P. h^Jt 24-hnur IC）P fluc.tuatinn at re.qtina ~.nnditinn.q wA.q InwAr in th~..~, n^ti~.nt.q

超声睫状体成形术治疗难治性青光眼的疗效及安全性

目的:探讨超声睫状体成形术治疗难治性青光眼的安全性及临床有效性。方法:前瞻性研究。收集2021-06/2022-10在我院就诊的难治性青光眼患者17例17眼,均行超声睫状体成形术治疗。随访6 mo,记录患者眼压、疼痛等级评分、降眼压药物使用、手术成功率以及并发症发生情况。结果:术后1 d(32.54±13.21 mmHg)、1 wk(22.38±11.98 mmHg)、1 mo(22.63±10.78 mmHg)、3 mo(26.05±9.17 mmHg)、6 mo(23.73±9.60 mmHg),均较术前眼压(51.98±7.80 mmHg)下降(均P<0.01);术后各时间节点眼压降低率依次为36.25%、57.10%、56.35%、49.16%、54.09%。术后疼痛等级评分较术前下降(P<0.01)。术后降眼压药物使用数量较术前减少(P=0.008)。术后6 mo时完全成功2眼(12%),部分成功11眼(65%),失败4眼(24%)。术后1 d发生前房炎性反应1眼(6%)、异物感2眼(12%)、结膜下出血2眼(12%)、结膜充血6眼(35%),所有症状均在1 wk内自行消失。术后10 d发生脉络膜脱离1眼(6%),经口服醋酸泼尼松片治疗1 mo后恢复。未见前房积血、瞳孔异位、虹膜黏连、黄斑水肿等严重并发症。结论:超声睫状体成形术治疗难治性青光眼可有效降低眼压,减轻患者眼部疼痛症状,并具有良好的安全性。

列线图构建原发性闭角型青光眼患者术后发生恶性青光眼的模型及验证

目的探讨原发性闭角型青光眼患者术后恶性青光眼的发生率及其危险因素,建立列线图模型并进行验证。方法选取2015年6月—2023年6月在西安交通大学第一附属医院眼科接受治疗的3389例原发性闭角型青光眼患者2100眼作为研究对象。术后6个月内出现恶性青光眼的97例(42眼)作为发生组,未出现恶性青光眼的3292例(2058眼)作为未发生组。收集两组患者的性别、年龄、合并糖尿病、高血压等一般资料;比较两组患者的术前晶状体厚度、前房深度、相对晶状体位置(LOWE系数)、高眼压情况、房角结构、眼轴长度、青光眼类型等;采用多因素一般Logistic回归模型分析术后发生恶性青光眼的危险因素;绘制列线图模型,并采用受试者工作特征(ROC)曲线评估模型的区分度;使用Bootstrap方法进行1000次重复采样,以验证列线图模型的预测效能。结果发生组年龄<50岁、术前持续高眼压、房角结构完全关闭占比均高于未发生组(P<0.05),晶状体厚度低于未发生组(P<0.05),眼轴长度短于未发生组(P<0.05),前房深度浅于未发生组(P<0.05)。多因素一般Logistic回归分析结果显示,术前眼压高[OR=24.179(95%CI:1.724,339.108)]、房角结构完全关闭[OR=59.427(95%CI:4.173,846.224)]、急性青光眼:[OR=15.507(95%CI:1.063,226.222)]是术后发生恶性青光眼的危险因素(P<0.05);年龄大[OR=0.022(95%CI:0.001,0.692)]、晶状体厚[OR=0.037(95%CI:0.003,0.493)]、眼轴长度长[OR=0.506(95%CI:0.264,0.971)]和前房深度深[OR=0.0004(95%CI:0.000,0.963)]是术后发生恶性青光眼的保护因素(P<0.05)。模型评估显示,ROC曲线下的面积为0.979,约登指数为0.871,敏感性为89.3%(95%CI:0.790,0.960),特异性为97.8%(95%CI:0.850,0.980),显示出良好的区分能力。校准曲线进一步证实了模型的高精确度,Bootstrap方法显示均方误差为0.032。结论本研究建立的原发性闭角型青光眼术后恶性青光眼是否发生的预测模型是可行的,在手术过程中应给予有这些危险因素的患者特别关注,以降低术后恶性青光眼的发生风险。