Clinical and molecular genetic study of a Chinese Han family with X-linked retinoschisis / 中华实验眼科杂志

Objective:To study the clinical phenotype and molecular genetic characteristics of a Chinese Han family with X-linked retinoschisis (XLRS), and to determine the associated gene variations.Methods:A pedigree investigation was performed.The clinical characteristics and pedigree analysis of a Han Chinese family line with XLRS was conducted in August 2021 at the Xiamen Eye Center Affiliated to Xiamen University.All patients and the carriers underwent comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, non-contact tonometer, slit lamp microscope, direct ophthalmoscope, and optical coherence tomography.The proband and some patients underwent medical optometry, fundus photography or wide-angle fundus photography, and electroretinogram examination.Peripheral venous blood samples were collected from the family members, and whole exome sequencing (WES) analysis was performed on the proband samples.For variants screened by WES, the expanded verification in other patients and normal persons in the family was carried out by Sanger sequencing.Multiple bioinformatic tools were used to analyze the pathogenicity of variants.This study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-KY-2021-012). Written informed consent forms were obtained from each subject or guardian of minors.CADD, FATHMM and other bioinformatics tools were used to analyze the pathogenicity of the variation sites.Results:The Han XLRS pedigree consisted of 8 individuals in 3 generations.Out of the 3 cases diagnosed with XLRS based on clinical evaluation, all were male.The mother of the proband was a carrier of related genes.There were 5 persons with normal phenotypes.There was no history of consanguineous marriages within the family, and the disease was shown to be intergenerational, which is consistent with the recessive inheritance of the X chromosome.None of the patients had a history of systemic disease or any other abnormal manifestations.The prevailing feature of ophthalmopathy was poor binocular vision since childhood.The proband and his younger brother had spoke split in the macula, and their grandfather showed atrophy of retinal nerve fibers.Genetic analysis revealed a hemizygous variation c. 214G>C: p.Glu72Gln in the RS1 gene in all the patients in this family.The proband's mother was heterozygous at this site, and all other phenotypically normal family members exhibited wild type at this site.This variant was predicted to be a deleterious variation and likely to cause disease based on bioinformatics analysis. Conclusions:The proband and patients in this Han Chinese family have the known c. 214G>C: p.Glu72Gln hemizygous variation of the RS1 gene and exhibit mild XLRS, which was consistent with the recessive inheritance of X chromosome.

Normal tension glaucoma: reconsideration and reevaluation / 中华实验眼科杂志

Normal tension glaucoma (NTG) is almost the most difficult type of glaucoma to diagnose.The difficulty lies in the lack of specificity of the symptoms and signs of glaucomatous optic neuropathy (GON), so the reevaluation of NTG is a new understanding of GON.As a subtype of primary open-angle glaucoma (POAG), NTG is difficult to accurately conceptualize.One of the reasons is that the intraocular pressure (IOP) is closely linked to the occurrence of GON in POAG but not in NTG.GON seems to be secondary to a number of local or systemic disorders, including vascular dysfunction in the optic nerve head induced by compression (elevated IOP) or ischemia, hypoxia, migraine, Flammer syndrome, intracranial hypotension, low body mass index, low estrogen levels, nocturnal hypotension, obstructive sleep apnea-hypopnea syndrome, Alzheimer disease, Parkinson disease, and genetic background, which may influence the flow in the radial peripapillary capillaries (RPCs) and the underfilling of RPCs causing retinal ganglion cell damage.In some cases, GON does not progress with systemic diseases under control, and these systemic diseases are not risk factors for NTG but may be the cause of GON (or GON is one of the manifestations of these diseases). If these causes are not excluded and NTG is diagnosed only on the basis of GON, chamber angle opening, and normal IOP, it is easy to cause misdiagnosis, and the complete exclusion of these diseases is short of clinical significance in practice.In conclusion, the diagnosis of NTG may not be made before the other ocular or systemic disorders capable of presenting with GON are ruled out, and the concept and diagnostic criteria of NTG should be reconsidered.

Genetic analysis of a Chinese family with cataract-microcornea syndrome / 中华实验眼科杂志

Objective:To analyze the clinical and molecular genetic characteristics of a Chinese family with congenital cataract-microcornea syndrome.Methods:The method of pedigree investigation was adopted.A Chinese Han family with congenital cataract-microcornea syndrome was recruited in Xiamen Eye Center of Xiamen University.All the family members received detailed ophthalmologic examination including the best corrected visual acuity, intraocular pressure measurement by handheld applanation tonometry, slit lamp biomicroscopy, color fundus photography, B-scan ultrasonography, corneal diameter, anterior segment optical coherence tomography, ultrasound biomicroscopy, corneal endoscopy, and corneal topography.Genomic DNA was extracted from peripheral venous blood from some patients and unaffected family members.Targeted high-throughput DNA sequencing was performed on the proband.The sequencing chip contained 188 known pathogenic genes related to lens abnormalities.Suspected pathogenic genes were verified by Sanger sequencing in phenotypically normal family members to identify the co-segregation and the disease-causing gene.Bioinformatics analysis was performed to analyze the pathogenicity of variants by REVEL.Conserved protein domains were analyzed by InterPro.Physicochemical property of the mutant protein was analyzed by ProtParam.The deleteriousness of the protein was predicted by PolyPhen-2.Homology of the variants in pathogenic gene was analyzed by NCBI website to compare the conservation among various species.This study followed the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.XMYKZX-LW-2009-003).Written informed consent was obtained from each subject prior to entering the study cohort.Results:There were 39 members of 4 generations in this family including 11 patients with an autosomal dominant inheritance pattern.Clinical features of the patients included congenital cataract and microcornea.No obvious abnormality was found in ophthalmic and general examination.A heterozygous mutation c. 61C>T in the CRYAA gene was found, resulting in the mutation of the amino acid from arginine to tryptophan (p.Arg21Trp) at position 21, consistent with co-segregation.The number of cationic cluster in the mutant protein decreased, and the hydrophilicity and stability were reduced.The variant was predicted to be deleterious and was highly conserved in multiple species. Conclusions:A novel heterozygous mutation c.61C>T p. Arg21Trp in CRYAA gene is considered as the causal gene of this family.It is the first time this variant has been reported in China.

Clinical and molecular genetics research of a Chinese Han family with Wagner syndrome / 中华实验眼科杂志

Objective:To explore the clinical features and pathogenic causes of a Chinese Han family with Wagner syndrome, and to analyze the relationship between VCAN gene mutation and patient phenotype. Methods:The method of family pedigree investigation was adopted.A Chinese Han family with Wagner syndrome in 3 generations including 13 family members was collected in Xiamen Eye Center of Xiamen University in January 2020, and 5 patients from 3 generations were diagnosed.All members underwent a comprehensive medical history collection and routine ophthalmological examinations, including visual acuity, intraocular pressure, slit lamp microscopy, and ophthalmoscopy to analyze the condition of anterior segment and fundus.Anterior segment photography, fundus photography, optical coherence tomography and ultrasound biological microscopy were carried out in the proband and some patients to analyze the condition of anterior segment, fundus and anterior chamber angle.The peripheral venous blood of all family members was collected for genomic DNA extraction, and pathogenic gene variation analysis for verification was through high-throughput target region capture sequencing and Sanger sequencing.Variants were scored using the American College of Medical Genetics and Genomics (ACMG) guidelines, and the structure and function of variants were predicted through PredictProtein.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xiamen Eye Center of Xiamen University (No.MR-35-22-002800).Written informed consent was obtained from each subject.Results:The Chinese pedigree with Wagner syndrome was in accordance with autosomal dominant inheritance pattern, and all patients had no history of systemic disease or other abnormal manifestations.The common ophthalmic features of the patients were abnormal suspensory ligament, premature cataract, vitreous cavity, vitreous condensation, veil-like proliferative membrane in the vitreous cavity, retinal choroid atrophy and thinning, tractional retinal detachment, and retinal pigmentation.The proband had binocular cataract surgery, and binocular intraocular lens dislocation occurred after the operation.Genetic analysis revealed that a heterozygous splice site variation c.9265+ 1G>A in the VCAN gene in this family was co-segregated with the disease phenotype and graded as a likely pathogenic variant by the ACMG guidelines.This variant base pair substitution could cause the formation of a protein product with 1 754 amino acids shorter, resulting in insufficient haploid dosage and severe reduction of glycosaminoglycan attachment sites, making the versican protein dysfunctional. Conclusions:It is the first time to report a Chinese family with Wagner syndrome in China, and it is confirmed that the family has a heterozygous variation in the VCAN gene c.9265+ 1G>A by molecular genetic analysis.

Social anxiety and associated factors among graduate students under the normalization of epidemic prevention and control / 中国学校卫生

Objective@#To understand social anxiety and relevant factors among graduate students under the normalization stage of COVID-19 epidemic prevention and control.@*Methods@#Using convenience sampling method, an online questionnaire survey on graduate students from 5 universities in Jiangsu Province was conducted. Measurements used in the survey includes General Self Efficacy Scale (GSES), General Alienation Scale (GAS), Interaction Anxiousness Scale (IAS) and self made survey for basic information and household living conditions.@*Results@#The overall score of graduate students self efficacy was (2.58±0.50). Average score was (30.68±6.22) for alienation, and (47.55±8.77) for interaction anxiety, with detection rate of social anxiety being 43.96%. Increased dependence on smartphones and electronic devices ( OR=1.86, 95%CI =1.32-2.61) and high alienation score (medium level: OR=2.06, 95%CI =1.45-2.92; high level: OR=5.19, 95%CI =1.00-27.00) were positively correlated with social anxiety. Increased communication with friends ( OR=0.65, 95%CI =0.47-0.90 and high self efficacy (medium level: OR= 0.37 , 95%CI =0.21-0.66; high level: OR=0.15, 95%CI =0.08-0.30) were negatively correlated with social anxiety.@*Conclusion@#At the normalization stage of COVID-19 epidemic prevention and control, social anxiety of graduate students is one of the mental health issues which need further attention. Participation in peer support helps prevent social anxiety through developing self efficacy, alleviating individual alienation, and reducing dependence on electronic devices among graduate students.

Interpretation of Guide to the Quality and Safety of Organs for Transplantation(6th edition): identification and referral of potential donors / 器官移植

Organ shortage is one of the important factors restricting the development of human organ transplantation. The identification and referral of potential donors determine the total scale of organ donation. Whether potential donors can be identified and referred is the most important reason for the difference of organ donation rates in different regions. This paper interprets the chapter of the identification and referral of potential donors in the Guide to the Quality and Safety of Organs for Transplantation (6th edition) issued by European Union in order to provide reference for the staff of organ procurement organization and related medical personnel in China and improve the organ donation rate in China.

Clinical study of single kidney transplantation from young pediatric donors after death: 86 cases report / 中华器官移植杂志

Objective By analyzing the perioperative management in our hospital to explore the clinical effect and safety of single kidney transplantation from deceased juveniles' donors.Methods We retrospectively analyze 86 cases of kidney transplantations from deceased juveniles' donors in our hospital from 2007 December to 2015 August.Results The success rate of the operations was 100％.The postoperative complications occurred as fellows:7 cases of acute rejection (8.14％);10 cases of drug intoxication (11.62％);21 cases of DGF (24.44％),4 cases of leakage of urine (4.65％),7 cases of lung infection (8.14％).Two cases (2.32％) died after the operation because of serious lung infection,and by corresponding treatment 47 cases recovered after 2-4 weeks.The creatinine level in 37 cases without any complications was 131.88 ± 44.20 μmol/L during discharge.Conclusion With strict selection,the organ from a deceased juvenile donor is safe and practicable.

Extra corporeal membrane oxygenation (ECMO) in deceased donors after brain death with severe hemodynamic instability allows to optimize the viability of livers and kidneys procured for transplantation / 中华器官移植杂志

Objective To observe the clinical effect of the maintenance for the liver and kidney function by extra corporeal membrane oxygenation (ECMO) in brain death donor with severe hemodynamic instability.Methods Ninety-nine brain death donors maintained by ECMO were followed up.The criteria for using the ECMO to protect the organ function were as follow:cardiopulmonary resuscitation history (cardiac compression ＞ 20 min);mean arterial pressure (MAP),for Adult ＜60-70 mmHg,for child ＜50-60 mmHg,and for infant ＜40-50 mmHg;cardiac index ＜2 L/(m2 ·min) (3 h);Large doses of vasoactive drugs,for doparnine 20μg/(kg·min),for (norepinephrine) epinephrine 1.0 μg/(kg· min) (3 h),and for oliguria ＜0.5 mL/(kg · h);blood biochemical indexes,moderate,severe impairment on acute hepatic and renal function;others,ST-T significant changes in electrocardiogram,and difficult to correct the metabolic acidosis (3 h).The organs were evaluated during their retrieval and as well their evolution after transplantation was evaluated.Results ECMO allowed for the maintenance of hemodynamic stability before organ procurement.A total of 99 cases receiving ECMO maintenance were collected,equal to100 ％ of the total donation cases (100％).198 kidneys,and 99 livers were procured from these donors meanwhile 15 kidneys and 42 livers respectively were discarded as theywere shown in a macroscopic evaluation.177 of the procured kidneys were transplanted.DGF of kidney transplantation was observed in 20.9％of the cases.Acute rejection incidence was 12.99％.Transplanted kidneys and recipient survival rate was 96.1％/99.3％ for one year,94.7％/97.8％ for 3 years,and 93.6/97.8％ for 4 years,respectively.There was no significant difference in patient or graft survival between the group with ECMO and the group without ECMO.Conclusion ECMO in the brain dead donors with severe circulatory dysfunction allows to avoid organ donors loss and obtain good quality kidneys and livers with excellent graft survival after transplantation.

Agreement of intraocular pressure measured by noncontact tonometer and Goldmann applanation tonometer : a Meta-analysis / 中华实验眼科杂志

Background Noncontact tonometer (NCT) is a common application in clinical ophthalmology,while its measured value is influenced by corneal parameter.In recent years,there existed some clinical trials discussing the agreement between NCT and gold standard Goldmann applanation tonometer (GAT),but there was still lack of evidence.Objective This study was to evaluate the agreement between NCT and GAT by applying evidence based medicine (EBM) method.Metbods A systematic literature retrieval was conducted from the MEDLINE,EMbase,CBM disc and CNKI database with the limitation of publishing time until June 2016.The literatures were screened according to the inclusion and exclusion criteria.The sample size,average age,sample characteristics and follow-up time were extracted.The value of intraocular pressure measured by NCT and GAT were analyzed.The overall effect size was analyzed using Review Manager 5.3 (from The Cochrane Collaboration) as weighted mean difference (WMD).There existed heterology in this study.Radom effect mode was used to evaluate and compare the difference between NCT and GAT value.Results Twenty four articles were retrieved.Six comparison studies incorporated with 478 eyes were included for Meta analysis.After random effects model was performed for correction.Intraocular pressure measured by NCT was 0.02 mmHg larger than that by GAT (1 mmHg =0.133 kPa).There was no significant difference in the measurement value of IOP between the two instruments (WMD =0.02,95％ CI:-0.59 to 0.63,P =0.95).Funnel chart method showed that literature publication bias existed in this study.Conclusions Normal persons' IOP obtained from NCT and GAT showed a good reproducibility.More comparison studies are needed to support this result.

Reconstruction and measurement of optic nerve sheath imaging in normal population with multi-slice spiral CT / 中华实验眼科杂志

Background Optical nerve damage of glaucomatous eyes is associated with intracranial pressure.Conventional method of evaluating intracranial pressure is to measure cerebrospinal pressure by lumber puncture.However,the measurement of intraorbital optical nerve parameters,a novel method of evaluating intracranial pressure,is introduced in this field.Objective This study was to measure and analyze the intraorbital optic nerve sheath diameter (ONSD) and cross sectional area (ONSA) in normal population using multi-slice spiral CT.Methods This study protocol was approved by Clinical Ethic Committee of Shenzhen Chinese Traditional Medical Hospital and followed Hersinki Declaration.Informed consent was obtained from each individual prior to any medical examination.One hundred and five eyes of 105 normal persons with normal cerebral CT image were enrolled in Shenzhen Chinese Traditional Medical Hospital from January 2012 to September 2013.Cerebral volume was scanned in all the individuals by 64 slice spiral CT.The brain images were obtained for the curve planar rebuilding of intraorbital optical nerve on image post-processing workstation.The maximum and minimum of ONSD and the ONSA in axial sections at 3,6,9,12 and 15 mm far away from globe wall were measured using a standardized technique to analyze the change of optical nerve parameters at different point locations.These parameters were compared in different gender or eyes.The correlation among age and the optical nerve parameters at 3 mm far away from globe wall was evaluated by multivariate regression analysis.Results The average maximal ONSDs were (6.24±0.47), (5.56±0.44),(5.18±0.43),(4.82±0.41) and (4.69±0.41) mm;the average minimal ONSDs were (5.56±0.50),(4.97± 0.41) ,(4.55±0.35),(4.26±0.39) and (4.10±0.40) mm;the average ONSAs were (27.68±4.40),(22.02±3.35) , (18.74± 2.75) , (16.34±2.72) , (15.40±2.68) mm2 at 3,6,9,12 and 15 mm far away from posterior eyeball wall,respectively, showing significant differences in the maximal/minimal ONSDs and ONSAs among the different point locations (F =218.329,215.906,246.924, all at P =0.001).No significant differences were found in the maximal/minimal ONSDs and ONSAs between male and female or between the right eyes and left eyes (gender:t=1.805,P=0.074;t=1.930,P=0.056;t=1.329,P=0.187;eyes:t=0.724,P=0.471;t=1.562,P=0.121;t=1.424,P=0.158).No significant correlations were seen between age and maximal/minimal ONSDs or ONSAs with the coefficients of 1.873,7.415 and-0.853 correspondingly (P =0.847,0.460,0.637).Conclusions Intraorbital section of optical nerve can be rebuilt using standardized technique after scanning of 64 slice spiral CT.The cross section of intraorbital optic nerve sheath is oval in shape and the optic nerve is thinning with the increase of distance far away posterior eyeball wall in normal populatuion.

Next generation sequencing based molecular genetic analysis of a Chinese Han family with autosomal retinitis pigmentosa / 中华实验眼科杂志

Background Retinitis pigmeutosa (RP) is a progressive inheritance disease.It is characterized by highly genetical and phenotypical heterogeneity.With the rapid development of genomics,new methods are applied to the genetic screening of RP.Objective This study was to characterize the clinical features of a Chinese family with autosomal RP and to screen the candidate genes.Methods Twelve members from this family were included in the study.All participants underwent complete ophthalmologic examinations.Targeted-capture next generation sequencing (NGS) based molecular genetic analysis was performed on two patients of this RP family(Ⅱ5,Ⅱ 7).The DNA sample from the two patients was separately sequenced using custom capture gene chip,which includes 59 retinal disease genes.The sequencing results were analyzed by bioinformatics technology.Identified variations were verified in the rest family members by PCR and Sanger sequencing.This study was approved by Ethic Committee of West China Hospital,and informed consent was obtained from the subjects.Results Four members of this family were diagnosed as RP,and the rest were asymptomatic.Missense mutation (c.3065T＞C,p.Phe1022Ser) in USH2A and missense mutation (c.1699G＞A,p.Ala1319Gly) in PDE6A were found in two patients (Ⅱ 5 and Ⅱ7).The variants were not co-segregated with the phenotype of this family.The causative mutation was not found by the targeted-capture NGS based eye disease chip,but it ruled out a large number of candidate genes for RP.Conclusions Our study suggests that targeted-capture NGS based eye disease chip can quickly detect mutations in known RP genes.It can be a new applicable and efficient method for molecular genetic analysis of ocular disease.

A pilot study of the relationship between retinal structural and functional damage in primary open-angle glaucoma / 中华实验眼科杂志

Background Application of available technology and objective indexes are very important for the early diagnosis,monitoring and therapeutic evaluation of primary open angle glaucoma (POAG).Many studies have determined retinal damage in structure and function in POAG.However,the study on the association of structural damage and functional abnormality in early POAG is still lack.Objective This study was to evaluate the relationship between structural and functional changes of retina in early stage of POAG.Methods A prospectively pilot study was performed under the approval of Ethic Committee of Shenzhen Eye Hospital from January 2011 to June 2013.Based on Helsinki Declaration,written informed consent was obtained from subject prior to entering the cohort.Ninety-five eyes of 95 POAG patients were included as the study group,and 41 eyes of 41 non-glaucoma subjects were enrolled at the same period as controls.The structural parameters of retinas were measured using RTVue-100 OCT and Cirrus HD-OCT respectively,including macular ganglion cell complex (GCC)-Avg thickness and peripapillary retinal neural fibril layer (RNFL)-Avg thickness;and the functional parameters of retinas were obtained by Humphrey visual filed analyzer and RETI scan 3.15 system respectively,including MD of visual field and PhNR of flash electroretinogram (F-ERG).The associations between the GCC or RNFL thickness and M D or amplitude of PhNR were evaluated by linear and curvilinear regression models.Results The MD,GCC-Avg,RNFL-Avg and PhNR amplitude were (-0.68±1.72)dB,(97.17± 4.82)μm,(102.51±8.74) μm and (49.61±11.01)μV respectively in the control subjects,and those in the POAG patients were (-10.82±9.87) dB,(75.07±12.29) μm,(69.09±12.96) μm and (28.38± 11.52) μV,showing significant differences between them (t =6.549,11.118,-15.061,9.956,all at P=0.001).The curvilinear regression model appeared to better describe the relationship between GCC thickness and MD (R2 =0.595,F=97.089,P＜0.001) ;while a linear regression model seemed to be better fit for the relationship between GCC thickness and amplitude of PhNR (R2=0.437,F=103.413,P＜0.001).RNFL thickness analysis showed the similar regression models with MD and amplitude of PhNR as GCC thickness,but R2 values were higher between the RNFL thickness and MD (R2 =0.606,F =101.666,P＜0.001) or amplitude of PhNR (R2 =0.454,F=54.983,P＜0.001).Conclusions Both GCC thickness and RNFL thickness show a curvilinear relationship with MD and a linear relationship with amplitude of PhNR.Goodness-of-fit of RNFL thickness is superior to GCC thickness.

Analysis of therapeutic effect and safety of target-dose metoprolol in the treatment of patients with diabetes mellitus with chronic heart failure

To explore the therapeutic effect and safety of target-dose metoprolol in treating chronic heart failure [CHF] patients complicated with diabetes mellitus [DM]. One hundred and fifty-four elderly patients were randomly divided into an observation group and a control group [n=77], which were treated with target-dose metoprolol and conventional therapy, and routinely treated respectively. The New York Heart Association [NYHA] classification, left ventricular end-systolic diameter [LVESD], left ventricular end-diastolic diameter [LVEDD], left ventricular ejection fraction [LVEF], 6-min walking distance and medication safety of the two groups were compared. Compared with the results before treatment, the NYHA classification, LVESD, LVEDD, LVEF and 6-minutes walking distance of both groups were significantly improved [P < 0.05], with significantly better results in the observation group than those in the control group after treatment [P < 0.05]. In the 6 months of follow-up, the incidence of cardiac events in the observation group [3.90%] was significantly lower than that of the control group [14.29%] [P < 0.05]. The levels of average fasting blood sugar and glycosylated hemoglobin in the groups showed no significant differences [P > 0.05]. Treating CHF patients complicated with DM with target-dose metoprolol can obviously boost the cardiac function and exercise tolerance, leading to satisfactory clinical therapeutic effect, high security and moderate tolerance

Roles and expressions of the NMDA receptor subunits (NR2A and NR2B) in visual cortex area of kittens with the normal visual development and anisometropic amblyopia / 生物医学工程学杂志

In order to understand the roles of the other subunits, we investigated expression of the NMDA receptor subunits (NR2A and NR2B) in visual cortex of normal and anisometropic amblyopia kittens with different ages in the present study. We examined the expressions of NR2A and NR2B in the visual cortex of the kittens by immunohistochemistry with polyclonal anti-NR2A antibody and anti-NR2B antibody, respectively. Using immunohisto-chemical Streptavidin Perosidase (SP) method, we observed the dynamic changes of NR2A and NR2B with microscope and computer-assisted image analyses. We found that NR2A and NR2B remained low expression after the peak of the critical period of kitten visual development; compared with normal group of the same age, NR2A expresses low. However, the difference is not significant for NR2B before maturation period of visual development. NR2B rises after the maturation period of visual development. According to this, the component of NR2A and NR2B can be affected by anisometropia. This research suggests that the difference of NR2A and NR2B expressions may affect the formation of amblyopia.

Effects of dexamethasone and latrunculin A on expression of protein in human trabecular meshwork cell / 眼科研究

Background Researches have demonstrated that dexamethasone (Dex) can induce the changes of the function and structure of trabecular meshwork cells,and latrunculin A (Lat A) can enhance the outflow of aqueous humour and therefore low the intraocular pressure.Objective The aim of the present study is to investigate the effects of Dex and Lat A on the expression of protein in human trabecular meshwork cells.Methods Human trabecular meshwork cells were primarily cultured in DMEM using expand culture method and the fifth generation of cells were used to this experiment.Dex and/or Lat A were added in medium as 10~(-6)mol/L Dex group(Dex treating for 24 hours),Dex+Lat A group(10~(-6)mol/L Dex+2mmol/L Lat A for 24 hours),Lat A group(2mmol/L Lat A for 24 hours) and DMEM culture group.Two dimensional gel electrophoresis(2 DE) was used to compare the protein expressions among these four groups.Subsequently protein spots with different intensity were selected for mass spectrometry analysis.Results Four gel patterns of two dimensional gel electrophoresis of human trabecular meshwork cells from Dex,Dex+Lat A,Lat A and control groups were obtained.A good isolated result for majority of proteins in human trabecular meshwork cells was found in all of the four groups.An obvious expression difference of proteins in human trabecular meshwork cells was seen among the different culture conditions.Twenty four kinds proteins were identified by GDPiMALDI TOF MS,including cytoskeleton related proteins,heat shock proteins,redox related proteins,and proteins participating in carbohydrate metabolism.The expressions of aldehyde dehydrogenase(ADLH)and Rab were increased in Lat A group and decreased in Dex group,but HSP27 and hCRMP2 showed the contrary outcome.Conclusion This study construct the pattern of protein expression in human trabecular meshwork cells by using 2 DE.Dex and Lat A impact the protein expressions in human trabecular meshwork cells.

Is glaucoma a central never system disease? / 眼科

Studies on glaucoma have been focused only on optic nerve damage and aqueous humor dynamic for many years. In recent years, with the advances in understanding of glaucoma and visual sciences, and the development of a neurological cross-discipline, new interdisciplinary problems have been raised. Notably, the question of whether glaucoma is only an optic nerve disease. Is it a disease that begins from the eye, and then involves the whole visual pathway? Or is it a particular central nervous system disease, which manifests itself in the eye? The answers to these problems are inconclusive so far, but there are reasons to believe that glaucoma is a disease with multi-level, multi-factor damage to the entire visual pathway involved. Its mechanisms are complex and involve cross-synaptic damage, visual pathway blood disorders, blood-brain barrier disorders, and so on. As we come to understand that glaucoma is an ocular and central never system neurodegenerative disease, we may better understand the pathogenesis of glaucoma and therefore establish comprehensive treatment strategies for this disease.