Gastrodin protects retinal ganglion cells through inhibiting microglial-mediated neuroinflammation in an acute ocular hypertension model

AIM：To investigate the neuroprotective effect of gastrodin on retinal ganglion cells（RGCs）in an acute ocular hypertension（AOH）rat model and to identify its possible mechanism.METHODS：AOH rat model was performed in a randomly selected eye by anterior chamber perfusion and either received an intraperitoneal injection with various concentrations of gastrodin or normal saline.After 2wk,the rats were sacrificed.Fluoro Gold was used to label survival RGCs.Immunostaining with anti-Iba1 in the retinal flat mounts to calculate the microglia density in the ganglion cell layer（GCL）.Changes in microglial cytokines,tumour necrosis factor-alpha（TNF-α）and inducible NO synthase（i NOS）were examined with Western blot and reverse transcriptionquantitative polymerase chain reaction.Expression levels of total and phosphorylated p38 mitogen activated protein kinase（MAPK）were determined by Western blot.RESULTS：Results showed that AOH induced significant loss of RGCs and severe microglia activation in the GCL.Besides,AOH increased the phosphorylation of p38 MAPK and promoted the release of microglial cytokines in the retinas.Intraperitoneal injection with dose-dependent gastrodin significantly reduced the loss of RGCs and inhibited retinal microglia activation,accompanied with the decreased expression levels of microglial cytokines and p38 MAPK phosphorylation.CONCLUSION：Gastrodin exerts a neuroprotective effect on RGCs in an acute glaucoma animal model viainhibiting microglia activation and microglial-mediated neuroinflammation.The finding demonstrates the potential application of gastrodin in the neuroprotective therapy of acute glaucoma and other retinal neurodegenerative diseases characterized by microglia activation and RGCs death.

Expression and role of autophagy related protein p62 and LC3 in the retina in a rat model of acute ocular hypertension

AIM: To investigate the expression and possible role of the autophagy related protein p62 and LC3 in the retina based on a rat model of acute ocular hypertension.METHODS: Fifty rats were randomized into five groups: control group A, B, C, and D. Groups A to D all received normal saline perfusion into the anterior chamber with pressure of 80 mm Hg for one hour, and retina tissue was obtained at 6, 12, 24 and 48 h after perfusion respectively, to investigate the activation of autophagy following ischemiareperfusion. The distribution and semi-quantification of autophagy related protein p62 and LC3 in the retina were detected using immunohistochemistry technique. The expression level of these two proteins was evaluated using Western blot.RESULTS: The number of retinal ganglion cells(RGCs) decreased with increasing reperfusion time, and significant reduction in the retinal thickness was observed 48 h after perfusion. In normal adult rats, LC3 protein was mainly expressed in the ganglion cell layer(GCL), and p62 protein was expressed in the nerve fiber layer(NFL), GCL, inner plexiform layer(IPL), inner nuclear layer(INL) and outer plexiform layer(OPL). In comparison to the control group, the expression level of LC3-II was higher in all the experimental groups(P<0.05), with the peak expression at 12 h after reperfusion. Additionally, the expression level of p62 was higher in all the experimental groups than the control(P<0.05, except for group A), with the peak level occurred 24 h after reperfusion. CONCLUSION: Both p62 and LC3 show low level and uneven expression in the retina of normal adult rats. Acute ocular hypertension can lead to upregulation of LC3-II and p62 expression in the retina. Autophagy flux is damaged 12 h after reperfusion, potentially resulting in further loss of RGCs.

Alpha B-crystallin improved survival of retinal ganglion cells in a rat model of acute ocular hypertension

Increased endogenous αB-crystallin protein levels have been shown to reduce cell apoptosis, although the effects of exogenous aB-crystallin protein remain poorly understood. The present study established an acute ocular hypertension model in the right eye of Sprague-Dawley rats. Fluorogold retrograde tracing and immunofluorescence methods showed that the number of retinal ganglion cells decreased in the right eyes and caspase-3 expression increased following acute ocular hypertension. Intravitreal injection of aB-crystallin in the right eye increased the number of retinal ganglion cells and reduced caspase-3 expression. Results demonstrated that exogenous αB-crystallin protein inhibited caspase-3 expression and improved retinal ganglion cell survival following acute ocular hypertension.

Activation of the ATP-P2X pathway by TRPV4 in acute ocular hypertension

AIM:To measure the expression of transient receptor potential cation channel subfamily V member 4(TRPV4)in the rat cornea and determine whether it is related to adenosine triphosphate(ATP)generation in a rat model of acute ocular hypertension(AOH).METHODS:Immunofluorescence staining of TRPV4,P2X2 receptor,P2X3 receptor,and(33-tubulin in rat corneal longitudinal sections and paved was performed to clearly display histological structures.Rat models of AOH and agonist/antagonist-treated groups were established and corneal ATP was measured using an ATP assay.The independent t-test and simple linear correlation model were adopted for statistical analyses.RESULTS:Immunofluorescence staining of rat cornea sections revealed that epithelial and endothelial membranes showed strong immunoreactivity for TRPV4 and P2X2 receptor and coexpression with(33-tubulin in the rat corneal epithelial layer.Corneal ATP was significantly higher in the AOH rat model than in the control(P<0.05)and apparently lower after pretreatment by applying eyedrops of TRPV4 antagonist RN1734 with 30-40 mm Hg intraocular pressure(IOP;P<0.05).A simple linear regression model showed a positive correlation between rat corneal ATP and IOP values(R^(2)=0.996,P=0.0134)from the normal IOP(113 mm Hg)to 40 mm Hg.At 10-40min after anterior chamber injection of GSK1016790A(0.01 mL,50 nmol/L in 0.9%NaCl),corneal ATP was significantly higher than in the control group(P<0.05),which peaked at 1Omin.The ATP concentration of the normal epithelium was higher than that of the endothelium in the AOH rat model and after anterior chamber injection of GSK1016790A(P<0.05).CONCLUSION:The ATP concentration in the AOH rat cornea is increased by TRPV4 activation.

Protective effects of human umbilical cord mesenchymal stem cells on retinal ganglion cells in mice with acute ocular hypertension

AIM:To observe the protective effect of human umbilical cord mesenchymal stem cells(huc MSCs)on retinal ganglion cel s(RGCs)injury in mice with acute ocular hypertension(AOH).METHODS:Fifty-six adult male C57 BL/6 mice were randomly divided into four groups:normal group,AOH group,huc MSCs group,normal saline(NS)group.Left eye of mice was induced by 90 mm Hg intraocular pressure for 1 h to establish AOH model.huc MSCs 1×105/μL,1μL or NS 1μL was injected into the vitreous body the next day.CMDil fluorescent dye was used to label the 3 rd generation of huc MSCs,for tracing the cells in the vitreous cavity of mice.Seven days after the model established,hematoxylin-eosin(HE)staining was used to observe the thickness of the inner retina layer in four groups.Numbers and loss rate of RGCs were evaluated by counting Brn-3 a positive cells stained by immunofluorescencein.RESULTS:On the 7 th day after AOH established,labeled huc MSCs were found in the vitreous cavity.HE staining showed that the thickness of retinal inner layer in AOH group was significantly lower than that in normal group and huc MSCs group(P<0.05),same as that in NS group(P>0.05).Compared with AOH group,the RGCs in normal group was significantly higher;RGCs number increased in huc MSCs group and the loss rate was lower(P<0.05).Injection of NS had no protective effect on RGCs.CONCLUSION:In AOH mouse model,vitreous injection of hucMSCs have shown a protection for RGCs.

A Study of Histology and Enzymatic Histochemistry on Rabbit's Retina in Acute Ocular Hypertension

The changes of activities of enzymes relating to energy metabolism in rabbit's retina in acute ocular hypertension were observed. The activities of succinate dehydrogenase and adenosine triphosphatase were found to be reduced, while the activities of the lactatic dehydrognease and glucose-6-phosphatase increased. The results revealed the metabolic disturbance of energy in retina after acute ocular hypertension might be the underlying factors relating to the defects of the functions and structures of the...

Effect of the Notch signaling pathway on retinal ganglion cells and its neuroprotection in rats with acute ocular hypertension

AIM： To explore the effect of the Notch signaling pathway on retinal ganglion cells（RGCs） and optic nerve in rats with acute ocular hypertension（OH）.METHODS： Totally 48 Sprague-Dawley（SD） rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 μL phosphate buffered solution（PBS） and another group of OH rats received a single intravitreal injection of 10 μmol/L γ-secretase inhibitor（DAPT）. Quantitative real-time polymerase chain reaction（qPCR） and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43（GAP-43）. The RGC apoptosis conditions were assessed by TUNEL staining.RESULTS： The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBSinjected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat.CONCLUSION： The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.

Melatonin alleviates pyroptosis of retinal neurons following acute intraocular hypertension

Glaucoma is a multifactorial optic neuropathy progressive characterized by structural loss of retinal ganglion cells(RGCs)and irreversible loss of vision.High intraocular pressure(HIOP)is a high risk factor for glaucoma.It has been reported that the manners of RGCs'loss are in-depth explored after acute HIOP injury,such as,apoptosis,autophagy and necrosis.However,pyroptosis,a novel type of pro-inflammatory cell programmed necrosis,rarely reported after HIOP injury.Researches also showed that melatonin possessing substantial anti-inflammatory properties.However,whether melatonin could alleviate retinal neurons death,especially pyroptosis,by HIOP injury is unclear.This study explored pyroptosis of retinal neurons and the effects of melatonin preventing retinal neurons form pyroptosis after acute HIOP injury.Establish acute HIOP model in rat by increasing the IOP and then reperfusion.

Outcomes of a non-diffractive extended depth of focus intraocular lens in patients with well-controlled glaucoma and ocular hypertension

AIM:To assess visual outcomes and satisfaction of a non-diffractive extended depth of focus(EDOF)intraocular lens(IOL)in individuals with ocular hypertension(OHT)and well-controlled mild glaucoma undergoing cataract surgery.METHODS:An investigator-initiated,single-center,prospective,interventional,noncomparative study conducted in Montreal,Canada.The study enrolled 31 patients(55 eyes)with OHT or mild glaucoma who received a non-diffractive EDOF IOL(Acrysof IQ Vivity).Participants underwent sequential cataract surgery with the Vivity IOL.Follow-up evaluations occurred at 1d,1,and 3mo postoperatively,assessing uncorrected distance,intermediate,and near visual acuity.Questionnaires(QUVID:Questionnaire for visual disturbances and IOLSAT:Intraocular lens satisfaction)were administered pre and post-operatively to measure visual disturbances and spectacle independence in various lighting.Safety parameters included intraocular pressure(IOP),glaucoma medications,spherical equivalence,mean deviation and pattern standard deviation or square root of lost variance on Octopus visual field.RESULTS:At 1 and 3mo postoperatively,significant improvements were observed in uncorrected distance and intermediate visual acuity.Spectacle independence was enhanced for distance and intermediate vision,especially in bright light settings.Spectacle-free intermediate vision was improved even in dim lighting.Visual disturbances,particularly glare symptoms,were reduced,and there was a notable decrease in IOP and glaucoma medication burden at 3mo.There was more hazy vision postoperatively with no impact on visual acuity and visual satisfaction.CONCLUSION:The non-diffractive EDOF lens improves distance and intermediate spectacle-free visual function in patients with OHT and well-controlled glaucoma.The findings highlight significant improvements in visual acuity,reduced glare,enhanced spectacle independence,and improved visual performance in different lighting conditions.

Acute upper gastrointestinal bleeding due to portal hypertension in a patient with primary myelofibrosis:A case report

BACKGROUND Acute upper gastrointestinal bleeding is a common medical emergency that has a 10%hospital mortality rate.According to the etiology,this disease can be divided into acute varicose veins and nonvaricose veins.Bleeding from esophageal varices is a life-threatening complication of portal hypertension.Portal hypertension is a clinical syndrome defined as a portal venous pressure that exceeds 10 mmHg.Cirrhosis is the most common cause of portal hypertension,and thrombosis of the portal system not associated with liver cirrhosis is the second most common cause of portal hypertension in the Western world.Primary myeloproliferative disorders are the main cause of portal venous thrombosis,and somatic mutations in the Janus kinase 2 gene(JAK2 V617F)can be found in approximately 90% of polycythemia vera,50% of essential thrombocyrosis and 50% of primary myelofibrosis.CASE SUMMARY We present a rare case of primary myelofibrosis with gastrointestinal bleeding as the primary manifestation that presented as portal-superior-splenic mesenteric vein thrombosis.Peripheral blood tests revealed the presence of the JAK2 V617F mutation.Bone marrow biopsy ultimately confirmed the diagnosis of myelofibrosis(MF-2 grade).CONCLUSION In patients with acute esophageal variceal bleeding due to portal hypertension and vein thrombosis without cirrhosis,the possibility of myeloproliferative neoplasms should be considered,and the JAK2 mutation test should be performed.

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.

Ocular hypertension in patients with central/hemicentral retinal vein occlusions： cumulative prevalence and management

AIM： To prospectively evaluate the cumulative prevalence and the management of ocular hypertension（OH） in patients with unilateral acute central/hemicentral retinal vein occlusions（C/HCRVOs） over the course of 3 y. METHODS： The study included 57 patients with unilateral acute C/HCRVOs. All patients underwent a comprehensive ophthalmological examination of both eyes. OH associated with C/HCRVO in patients showing a score 〉5% for the risk of conversion to primary open angle glaucoma（POAG） was treated with OH medication. The treatment aimed for a decrease in intraocular pressure（IOP） to 〈21 mm Hg with a 〉22% reduction from the initial values. The cumulative prevalence of OH and the effectiveness of treatment assessed by the cumulative prevalence of conversion from OH to POAG, were estimated. RESULTS： Fifteen patients had OH associated with C/HCRVOs, the cumulative prevalence of OH was 29.4%（95% confidence interval, 16.9-41.9）. The mean value of the risk score of OH conversion to POAG for the 5 subsequent years was 11.7%±5.4%. The IOP significantly decreased from 25.67±2.16 mm Hg to 18.73±2.96 mm Hg. None of the OH patients converted to POAG during the follow-up period. CONCLUSION： The increased cumulative prevalence of OH in C/HCRVO patients indicates that OH is a risk factor for the appearance of venous occlusion. Patients with OH associated with C/HCRVO must be considered to be at high risk for conversion to POAG. Treatment with OH medications prevented conversion to POAG during the 3-year follow-up.

Intraocular pressure modifications in patients with acute central/hemicentral retinal vein occlusions

Intraocular pressure(IOP)modifications in patients with acute central/hemicentral retinal vein occlusions(RVOs)consist in IOP reductions and increases.The IOP reduction is due to a transitional hyposecretory phase of the aqueous humor,that increases gradually until 3 mo after the venous occlusion onset,and then finally disappears after month 4 th.The IOP increases lead to the ocular hypertension and glaucoma.The possible pathogenetic correlations between ocular hypertension/glaucoma and acute central/hemicentral RVOs have been classified into three groups:1)the venous occlusion precedes the ocular hypertension/glaucoma causing neovascular glaucoma and secondary angle-closure glaucoma without rubeosis;2)the ocular hypertension and the glaucoma precede the venous occlusion and favor its appearance(ocular hypertension,primary angle-closure,primary angle-closure glaucoma,and open angle glaucomas);and 3)the venous occlusion and the ocular hypertension/glaucoma are mostly age dependent appearances due to common vascular and collagen alterations,lacking a causal connection between the 2 conditions.

c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice:a possible target to reduce ganglion cell apoptosis

Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase （JNK） participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by pho- tocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

Clinical relevance of the glucocorticoid receptor gene polymorphisms in glucocorticoid-induced ocular hypertension and primary open angle glaucoma

AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma(POAG) patients show this phenotype.Glucocorticoid receptor(GR) regulates C responsiveness in trabecular meshwork(TM) cells. In this study, single nucleotide polymorphism(SNP) genotyping was used to determine whether there are differences in the Bcl I(rs41423247) and N363S(rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension(GIOH)populations.METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the Bcl I and N363 S polymorphisms were screened using real-time polymerase chain reaction(RT-PCR)-restriction fragment length polymorphism(RFLP) analysis. Frequencies of the Bcl I and N363 S polymorphisms were determined and compared using Fisher’s exact test and the Chi-squared test.RESULTS: Only the Bcl I polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363 S polymorphism was found in the study subjects.CONCLUSION: The Bcl I polymorphisms in GR gene had no association with GIOH and POAG patients, and N363 S polymorphism might not exist in the Chinese Han population. Therefore, the Bcl I polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.

The assessment of structural changes on optic nerve head and macula in primary open angle glaucoma and ocular hypertension

AIM：To assess morphological changes in macula, retinal nerve fiber layer （RNFL） and optic nevre head （ONH） of cases with primary open angle glaucoma （POAG） and ocular hypertension （OH） with spectral domain optic coherence tomography （OCT）.METHODS：This study included 109 eyes from 62 POAG patients, 50 eyes from 30 OH patients, and 101 eyes from 53 healthy volunteers. Data gained by OCT were compared with perimetry indexes. ONH, RNFL and macula analysis were performed for all subjects. Rim area, disc area,average cup/disc （C/D） ratio, vertical C/D ratio, cup volume data were recorded during ONH analysis. Average RNFL thickness and the thickness of four quadrants （superior,inferior, nasal and temporal） was established in microns.In total, nine macular quadrants involving the foveal region mentioned in the Early Treatment Diabetic Treatment Study（ETDRS） template were measured, and average macular thickness and macular volume data were recorded during macula analysis. Differences between groups were evaluated with the one-way ANOVA test. Tukey’s multiple comparison test was performed to detect difference between groups.Receiver-operating characteristic （ROC） analysis was done for early stage POAG patients to establish sensitivity and specificity of chosen parameters in early stage POAG.Area under the receiver operating characteristic （AUROC）values were calculated to compare ROC areas.RESULTS：Statistically significant differences were found in all ONH parameters, except optic disc area. Neuroretinal rim area was identified as the parameter with the highest difference between groups （F=21.72, P〈0.05）. The highest correlation between ONH parameters and perimetry was observed at neuroretinal rim region （r=0.487）. Inferior RNFL thickness was established as the parameter with the highest difference between groups among RNFL parameters. In the mean of all glaucoma patients, the highest correlation between data handled with OCT and mean deviation was observed in RNFL thickness. Average macular thickness was detected as the parameter with the highest difference between groups among macular parameters. The highest correlation between macula parameters and perimetry indexes was observed between average macular thickness and perimetry indexes （r=0.514）.CONCLUSION：Although the assessment of ONH and the analysis of macular thickness are important in diagnosis and treatment, RNFL assessment is the most valuable parameter.

Ultrasound biomicroscopic evaluation of anterior segment cysts as a risk factor for ocular hypertension and closure angle glaucoma

AIMTo investigate the relationship between the ultrasound biomicroscopic (UBM) features of anterior-segment cysts (ASCs) and increased intraocular pressure (IOP) as a risk factor for closed-angle glaucoma (CAG).

Effect of erythropoietin on the expression of HIF-1 and iNOS in retina in chronic ocular hypertension rats

AIM: To research the effect of erythropoietin (EPO) to the HIF-1\iNOS signal transduction path in retina in chronic ocular hypertension rat. METHODS: One hundred and twenty Wistar rats were divided into 12 groups randomly. Two episcleral veins were coagulated unilaterally in rats with electric coagulator to establish the glaucoma model. PT-PCR and Western Blot analysis were used to examine the expression of Caspase-9 genes in retina. And the changes of ERG-b wave before and after were detected using EPO. RESULTS: In EPO drug treatment group, the amplitude of ERG-b wave of retina restored remarkably. There was significant difference between two groups (P< 0.05). The expression of HIF-1\iNOS mRNA and protein in EPO drug treatment group were weakened remarkably. It was statistically different compared with the non-drug treatment group. CONCLUSION: One of protect mechanisms of EPO to injured retina caused by chronic intraocular hypertension is through HIF-1\iNOS signal conduct path.

TGF-β_1 in retinal ganglion cells in rats with chronic ocular hypertension: its expression and anti-apoptotic effect

AIM: To investigate the anti-apoptotic effect of transforming growth factor beta-1 (TGF-β1) on chronic ocular hypertension. METHODS: The expression of TGF-β1 in retinal ganglion cells (RCGs) was measured using the immunohistochemiscal S-P method and real-time PCR in the normally control group, the ocular hypertension group (experimental group A), the ocular hypertension plus antibody intervention group (experimental group B) and the ocular hypertension plus antigen intervention group (experimental group C) at 1, 2, 3 and 4 weeks postoperatively. The count of apoptotic RCGs was measured using the TUNEL method. RESULTS: The expression of TGF-β1 was significantly higher in experimental group C than that in other three groups (P<0.05). The expression was the lowest in experimental group B (4.17%). A statistically significant difference was noted between the four groups (P <0.01). The count of apoptotic RCGs was statistically significantly lower in experimental group C than that in the experimental groups A and B (P <0.01). A statistically significant difference was noted in the count of apoptotic RCGs between these three experimental groups (P <0.01). CONCLUSION: TGF-β1 can inhibit the apoptosis of RCGs in rats with chronic ocular hypertension.

Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of0.005% latanoprost and 0.5% timolol(FCLT) vs their individual components for primary open angle glaucoma(POAG) and ocular hypertension(OHT).· METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials(RCTs) and cross-over studies were included. The control groups were the monotherapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure(IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:Thepost-interventionmeanIOPofFCLTwas significantly lower compared to timolol [mean difference(MD)-2.92, 95%CI-3.28 to-2.55, P 【0.00001] and latanoprost(MD-1.11, 95%CI-1.51 to-0.72, P 【0.00001). The postintervention IOP fluctuation was also significantly lower compared to timolol(MD-0.88, 95%CI-1.23 to-0.53, P 【0. 00001) and latanoprost( MD- 0. 63, 95 % CI- 1. 04to-0.22, P =0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol(UFCLT)(MD1.10, 95% CI 0.81 to 1.39, P 【0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT(MD 0.34, 95% CI-0.01 to 0.69, P =0.06).There was no statistical difference for the incidence ofvisual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the monotherapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.