CD44分子与原发性开角型青光眼

本综述了细胞黏附分子CD44与原发性开角型青光眼(POAG)发病机制的关系。CD44分子参与了POAG的病理过程，它可引起小梁细胞结构和功能异常、细胞凋亡以及细胞数目减少，并能影响小梁细胞的内环境(小梁网细胞外基质和房水)稳定，以及对视网膜神经节细胞具有毒性作用。     

CD44分子与原发性开角型青光眼

本文综述了细胞黏附分子CD44与原发性开角型青光眼(POAG)发病机制的关系。CD44分子参与了POAG的病理过程,它可引起小梁细胞结构和功能异常、细胞凋亡以及细胞数目减少,并能影响小梁细胞的内环境(小梁网细胞外基质和房水)稳定,以及对视网膜神经节细胞具有毒性作用。     

反义CD44基因转染对人眼小梁细胞合成细胞外基质的影响

目的：观察反义CD44基因转染对人眼小梁细胞合成细胞外基质的影响,探讨黏附分子CD44在原发性开角型青光眼(primary open angle glaucoma, POAG)发病过程中可能的作用。 方法：采用硫代修饰的CD44反义寡核苷酸,通过脂质体介导转染体外培养的人眼小梁细胞,免疫组织化学染色观察CD44反义寡核苷酸对小梁细胞合成胶原蛋白Ⅰ型、层黏附蛋白的影响,放射免疫法观察CD44反义寡核苷酸对小梁细胞合成透明质酸的影响。 结果：CD44反义寡核苷酸对人眼小梁细胞合成胶原蛋白Ⅰ型、层黏附蛋白起促进作用,且呈浓度依赖性,浓度越高促分泌作用越强,但对小梁细胞合成透明质酸起抑制作用,浓度越高抑制作用越明显。 结论：CD44反义寡核苷酸封闭CD44基因表达后人眼小梁细胞合成胶原蛋白Ⅰ型、层黏附蛋白增加而合成透明质酸减少。黏附分子CD44可能通过影响小梁细胞合成细胞外基质功能参与了POAG发病过程。     

sCD44分子与原发性开角型青光眼

随着对可溶性黏附分子CD44(sCD44)生物学功能和化学本质的深入认识,人们发现sCD44分子参与了原发性开角型青光眼(primary open-angle glaucoma,POAG)的病理过程,它可以引起小梁网细胞结构和功能异常、细胞凋亡,其对视网膜神经节细胞具有毒性作用.文中就sCD44分子与POAG关系的研究进展作一综述.     

可溶性CD44分子对原发性开角型青光眼患者小梁网细胞凋亡的影响

目的 探讨不同浓度的可溶性CD44分子(soluble CD44,sCD44)对原发性开角型青光眼(primary open-angle glaucoma,POAG)患者小梁网细胞凋亡的影响,以及研究sCD44与POAG发病的关系.方法 采用组织块培养法原代培养POAG患者小梁网细胞,取传3代的小梁网细胞分别加入含sCD44终浓度为0ng/ml(对照组),l ng/ml,5 ng/ml,10 ng/ml,25 ng/ml,50 ng/ml的无血清培养基,分别培养24h后收集细胞,采用CCK-8法、荧光显微镜和流式细胞仪法,研究sCD44对POAG患者小梁网细胞凋亡的影响.结果 通过CCK-8法检测发现:随着sCD44终浓度的增加,sCD44对POAG患者小梁网细胞的抑制作用增强,且各实验组与对照组及各实验组之间相比差异有统计学意义(P＜0.05);通过荧光显微镜观察显示随着sCD44终浓度的增加,早期和晚期凋亡细胞明显增多;通过流式细胞仪法检测sCI44终浓度为l ng/ml,5 ng/ml,10 ng/ml,25 ng/ml,50 ng/ml实验组小梁网细胞凋亡率分别为10.73±0.02,17.33±0.03,21.15±0.02,25.13±0.03,30.00±0.03,均高于对照组小梁网细胞凋亡率2.56±0.02,且各实验组与对照组及各实验组之间相比差异有统计学意义(P＜0.05).结论 sCD44在一定浓度范围内可以抑制POAG患者小梁网细胞的增殖,促进细胞的凋亡,并且呈现一定的剂量依赖性,sCD44可能通过作用于小梁网细胞间接参与POAG的发病过程.     

CYP1B1基因突变与原发性开角型青光眼发病关系的研究进展

原发性青光眼包括原发性开角型青光眼（POAG）、原发性闭角型青光眼（PACG）及原发性婴幼儿青光眼（PCG）.目前认为原发性青光眼的发病是遗传因素、环境因素、生活习惯等多种因素综合作用的结果,其中遗传因素,尤其是基因突变,在青光眼的发病过程中起着重要作用.自1997年发现CYP1B1基因为PCG的致病基因以来,关于CYP1B1基因突变与青光眼发病关系的研究成为青光眼遗传和基因研究的热点.随着研究的逐渐深入,许多学者认为CYP1B1基因也是POAG致病基因的候选基因.本研究对近十余年来对CYP1 B1基因的结构和功能以及CYP1B1基因突变与POAG发病及进展关系的研究进展进行总结.     

原发性青光眼外周血淋巴细胞CD44和CD54检出的临床意义

目的研究原发性青光眼发生与发展过程中外用血淋巴细胞CD44及CD54表达量及其临床意义。方法28例原发性青光眼及28例健康人外周静脉血，经淋巴细胞分离、CD44-FITC及CD54-FITC免疫反应、流式细胞分析仪测定CD44及CD54表达量，并行统计学分析。结果原发性闭角型及开角型青光眼患者外周血淋巴细胞CD44及CD54表达量明显升高，与正常人比较，P＜0．01，差异有非常显著性意义。结论粘附分子CD44及CD54表达量升高与原发性青光眼发生与发展过程相关。CD44及CD54可能参与原发性青光眼发生与发展过程。     

单眼发病的原发性开角型青光眼黄斑脉络膜厚度及影响因素初探

目的:初步探讨原发性开角型青光眼（POAG）单眼发病患者黄斑中心凹下脉络膜厚度（SFCT）与其对侧眼和健康人的差异及其影响因素。方法:横断面研究。收集2018年9月至2019年9月就诊于首都医科大学附属北京同仁医院青光眼门诊确诊为POAG的单眼发病、对侧眼正常的患者（POAG组）以及健康志愿者（健康对照组）。对所有参与...     

反义寡核苷酸封闭CD44基因表达对小梁细胞吞噬及聚集功能的影响

目的观察CD44反义寡核苷酸封闭CD44基因表达对人眼小梁细胞吞噬、聚集功能的影响,进一步探讨黏附分子CD44在原发性开角型青光眼(primary open angleglaucoma,POAG)发病过程中可能的作用。方法取意外死之后行角膜移植供体眼小梁细胞,实验分空白对照组,2.0μmol·L-1正义寡核苷酸,0.5μmol·L-1、1.0μmol·L-1、2.0μmol·L-1反义寡核苷酸共5组,采用硫代修饰的CD44反义寡核苷酸,通过脂质体介导转染体外培养的人眼小梁细胞。以乳胶微粒为标记定量观察CD44反义寡核苷酸封闭CD44基因表达对人眼小梁细胞吞噬功能的影响,计数法观察CD44反义寡核苷酸封闭CD44基因表达对人眼小梁细胞聚集功能的影响。结果3种浓度的CD44反义寡核苷酸处理的小梁细胞吞噬微粒数分别为58.2±18.8、47.5±16.9、34.9±16.3,明显低于对照组的75.9±13.4(P<0.05)及CD44正义寡核苷酸组的74.0±11.8(P<0.05),且呈浓度依赖性。而对照组与CD44正义寡核苷酸组间比较差异无统计学意义(P>0.05)。3种浓度的CD44反义寡核苷酸处理各组出现细胞聚集阳性平均次数分别为(24.50±5.26)次、(16.30±3.77)次、(9.25±1.71)次,明显低于对照组的平均(32.00±3.37)次(P<0.05)和CD44正义寡核苷酸组的(33.25±5.32)次(P<0.05),且呈浓度依赖性,而CD44正义寡核苷酸组与对照组比较差异无统计学意义(P>0.05)。结论CD44反义寡核苷酸封闭CD44基因表达后人眼小梁细胞吞噬功能降低以及小梁细胞的聚集功能受到抑制,黏附分子CD44可能通过影响小梁细胞的吞噬以及聚集功能参与了POAG发病过程。     

原发性开角型青光眼对皮质激素、肾上腺素敏感反应及其与HLA抗原间的关系

Becket及Kass等近年来发表了一系列有关原发性开角型青光眼(Primary open-angle glautcoma,简称POAG)对皮质激素和肾上腺素的高敏反应及与HLA-B_7、B_(12)等抗原相互关系的文献,认为POAG的这些特征与临床上青光眼视野进展有关的各项危险指标如阳性家族史、高眼压,较大的C/D比率(C/D>0.3)等有不同程度的联系。Becker等人对POAG发病机理在细胞和分子水平的研究和遗传方式的探讨上已自成一个学派。在近代有关POAG发病的基础研究中已成为一个争论的焦点。本文着重介绍近十年来该     

Aqueous humor in primary open-angle glaucoma contains an increased level of CD44S.

PURPOSE: To determine whether the cell adhesion molecule CD44, the principal receptor of hyaluronan, is altered in the aqueous humor and the anterior segment of patients with primary open-angle glaucoma (POAG). METHODS: The trabecular meshwork (TM), iris, ciliary body, and sclera of POAG and age-matched control eyes preserved in ethanol were microdissected and subjected to 1% Triton X-100 solubilization at 4 degrees C. Western blot analysis was performed using monoclonal antibodies that recognize either CD44H (hematopoietic; extracellular domain) or CD44S (soluble ectodomain). The concentration of soluble CD44S in aqueous and microdissected tissues was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA of soluble CD44S of aqueous from eyes of patients with POAG indicated that the concentration of soluble CD44S is increased in comparison with that of aqueous from normal eyes (P < 0.0003). Western blot analysis and densitometry of POAG iris and ciliary body revealed a statistically significant increase in the Triton X-100 extraction of CD44H. The predominant increases were in the 180-kDa (P < 0.001) and the 85-kDa (P < 0.001) forms. ELISA of soluble CD44S indicated that the concentration is statistically decreased in iris (P < 0.05), ciliary body (P < 0.001), and TM (P < 0.005) of POAG eyes. CONCLUSIONS: Increased amounts of soluble CD44S in POAG aqueous and Triton X-100-solubilized CD44H characterized POAG in the iris and ciliary body. These soluble CD44 isoforms may influence the activity of the transmembrane CD44H by acting as inhibitors of CD44H and, thereby, adversely influence the cell survival of TM and retinal ganglion cells in POAG.     

Erythropoietin and soluble CD44 levels in patients with primary open‐angle glaucoma

Purpose: To investigate the levels of erythropoietin (EPO) and soluble CD44 (sCD44) in the aqueous and plasma of human eyes with primary open‐angle glaucoma (POAG), and to correlate their concentration with severity of glaucoma. Methods: A total of 30 patients with POAG and 25 patients with senile cataract (control group) of matched age and gender were included in the study prospectively. Aqueous samples were obtained by paracentesis from glaucoma and cataract patients who were undergoing elective surgery. Aqueous and corresponding plasma samples were analysed for EPO and sCD44 concentrations by enzyme‐linked immunosorbent assay. Results: The EPO and sCD44 levels were significantly higher in aqueous of POAG patients with respect to the comparative group of cataract patients (P < 0.001). No significant difference in the levels of EPO and sCD44 in plasma of POAG and cataract patients. A high positive correlation was found between EPO and sCD44 in aqueous of POAG patients (P < 0.001). Significant correlation was found between EPO or sCD44 levels and severity of visual field loss in mild and moderate stages (P < 0.001). Conclusion: Increased levels of aqueous EPO and sCD44 may be associated with POAG. In addition, EPO and sCD44 may be useful proteins levels in aqueous of POAG patients as a result of glaucoma damage and not a cause. EPO and sCD44 concentrations in aqueous are a possible biomarkers for visual field loss in patients with POAG.     

Aqueous humor sCD44 concentration and visual field loss in primary open-angle glaucoma

PURPOSE: To correlate aqueous humor soluble CD44 (sCD44) concentration, visual field loss, and glaucoma risk factors in primary open-angle glaucoma (POAG) patients. METHODS: Aqueous samples were obtained by paracentesis from normal and glaucoma patients who were undergoing elective surgery and analyzed for sCD44 concentration by enzyme-linked immunosorbent assay. RESULTS: In normal aqueous (n=124) the sCD44 concentration was 5.88+/-0.27 ng/mL, whereas in POAG aqueous (n=90) the sCD44 concentration was 12.76+/-0.66 ng/mL, a 2.2-fold increase (P<0.000001). In POAG patients with prior successful filtration surgery (n=13), the sCD44 concentration was decreased by 43% to 7.32+/-1.44 (P=0.001) in comparison with POAG patients without filtration surgery; however, the sCD44 concentration in the prior successful filtration subgroup with no medications and normal intraocular pressure was 12.62+/-3.81 (P=0.05) compared with normal. The sCD44 concentration of normal pressure glaucoma patients was 9.19+/-1.75 ng/mL, a 1.6-fold increase compared with normal (P=0.02). Race and intraocular pressure pulse amplitude were significant POAG risk factors in this cohort of patients. In both normal and POAG patients with mild and moderate visual field loss, sCD44 concentration was greater in African Americans than in whites (P=0.04). CONCLUSIONS: sCD44 concentration in the aqueous of POAG patients correlated with the severity of visual field loss in all stages in white patients and in mild to moderate stages in African American patients. sCD44 concentration in aqueous is a possible protein biomarker of visual field loss in POAG.     

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma

PURPOSE: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG). METHODS: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively. The bioactivity of hypophosphorylated sCD44 was tested in cell culture and HA affinity columns. RESULTS: Two-dimensional Western blot analysis revealed that the representative pI of the 32-kDa sCD44 was 6.96 +/- 0.07 in POAG versus 6.38 +/- 0.08 in normal (P < 0.0004). Enzymatic dephosphorylation of sCD44 resulted in a basic shift in the pI. The normal aqueous humor sCD44 was positive for serine-threonine phosphorylation; however, POAG sCD44 was hypophosphorylated. Hypophosphorylated sCD44 was more toxic to TM and RGC cells than standard sCD44, and hypophosphorylated sCD44 had decreased affinity to HA, particularly with increased pressure. CONCLUSIONS: POAG aqueous is characterized by posttranslational change in the pI of sCD44 and hypophosphorylation, which clearly distinguished POAG from normal aqueous humor. The high toxicity and low HA-binding affinity of hypophosphorylated sCD44 may represent specific pathophysiologic features of the POAG disease process.     

Relationship between optic nerve head microcirculation and visual field loss in glaucoma

PURPOSE: To study the relationship between optic nerve head blood flow velocity and visual field loss in patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). METHODS: This study included 44 eyes of 44 patients with POAG and 44 eyes of 44 patients with NTG. To evaluate optic nerve head blood flow velocity, the square blur rate (SBR) was measured by means of laser speckle flowgraphy. The correlation between SBR and Humphrey visual field indices was evaluated with linear regression analysis. RESULTS: In the NTG group, the average SBR at the superior and inferior temporal neuroretinal rim was positively correlated with mean deviation (MD) (r = 0.349, p = 0.020). The SBR at the superior or inferior temporal neuroretinal rim was positively correlated with the sum of the total deviations in the corresponding hemifields (r = 0.299, p = 0.049; r = 0.354, p = 0.019, respectively). The correlations between SBR and MD did not differ statistically between the NTG and POAG groups; however, no significant correlation between SBR and visual field indices was observed in the POAG group. CONCLUSION: These results suggested that the change in the circulation of the optic nerve head may be related to visual field damage in the NTG group but may be less involved in visual field damage in the POAG group.     

Soluble CD44 is cytotoxic to trabecular meshwork and retinal ganglion cells in vitro

PURPOSE: Current glaucoma research targets neuroprotective therapies for retinal ganglion cells (RGCs) in primary open-angle glaucoma (POAG). The purpose of this study was to determine whether the 32-kDa ectodomain fragment of CD44-soluble CD44 (sCD44)-which is increased in the aqueous of patients with POAG, affects RGC and trabecular meshwork (TM) cell survival in vitro. METHODS: sCD44 was isolated from human or fetal calf serum (FCS) by urea solubilization and immunoprecipitation. A transformed rat RGC-like cell line (RGC-5), human and bovine TM cells, and control cells were grown in Dulbecco's modified Eagle's medium containing 10% FCS until confluent and then were incubated in medium containing 0.1% FCS and treated with various doses of purified sCD44 and 17-alpha-methyl testosterone (17-alpha-MT). The cytotoxicity of sCD44 was verified by heat-inactivation, pretreatment with a pan-caspase inhibitor, and coadministration of anti-CD44 neutralizing antibody or hyaluronic acid (HA). Cell viability was assessed by trypan blue staining, cell counting, and phase-contrast microscopy. RESULTS: There was a statistically significant dose- and time-dependent decrease in the number of cells and viability in the RGC-5 and TM cells treated with sCD44. Within 12 hours of sCD44 treatment, RGC-5 and TM cells displayed cell rounding, detachment, and swelling. sCD44-induced cell death was cell specific. Smooth muscle cells were resistant to sCD44, whereas human cortical neuronal-like cells were susceptible to sCD44 after 24 hours, but recovered. The cytotoxicity of sCD44 was blocked by heat-inactivation, pretreatment with a pan-caspase inhibitor, or coadministration of anti-CD44 antibody or HA. 17-alpha-MT prevented sCD44 cytotoxicity in both RGC-5 and TM cells. CONCLUSIONS: The results indicate that exogenous sCD44 adversely affects RGC-5 and TM cell survival in vitro by activating proapoptotic pathways.     

Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan.

Clinical features of capsular glaucoma during a recent 15-year period were compared with those of primary open-angle glaucoma (POAG). Out of 1623 new glaucoma patients, 263 patients (16.2%) were capsular glaucoma and 268 (16.5%) were POAG. The patients with capsular glaucoma were older than the patients with POAG. The former had higher intraocular pressure, lower visual acuity, more advanced visual field change and heavier trabecular pigmentation than POAG patients at the time of initial examination. These findings suggest that capsular glaucoma is more difficult to manage than POAG and that the prognosis is poorer than for POAG. Pseudoexfoliative material was found on the pupillary border in 98.3%, on the central lens surface in 46.1%, and on the peripheral lens surface in 72.3%. Though 190 of 263 patients with capsular glaucoma (73.9%) were unilateral cases, 38.9% of the fellow eyes had some abnormalities related to glaucoma. Phakodonesis was found in 10% of patients with capsular glaucoma. This finding suggests that the presence of capsular glaucoma might be a risk factor in cataract surgery.     

T cell subsets and sIL-2R/IL-2 levels in patients with glaucoma

PURPOSE: We hypothesize that cellular immunity may have a previously unrecognized role in glaucomatous optic neuropathy. The purpose of this study is to analyze subsets of T cells and the levels of cytokine IL-2 and the soluble IL-2 receptor in peripheral blood from patients with normal pressure glaucoma (NPG) or primary open angle glaucoma (POAG) in comparison to age-matched control subjects. METHODS: In this study, 38 patients (20 NPG; 18 POAG) and 19 controls were included. sIL-2R and IL-2 were assayed by ELISA. T cell subsets were analyzed by flow cytometry and lymphocyte proliferation was used to measure the reactive ability of T cells to phytohemagglutinin (PHA). RESULTS: The frequency of CD8(+)HLA-DR(+) lymphocytes were increased in patients with NPG (P = 0.008), and CD3(+)CD8(+) lymphocytes increased in both NPG (P = 0.03) and POAG patients (P = 0.0004). CD5(+) lymphocytes were higher only in POAG patients (P = 0.0012). In comparison to controls, the ratio of CD4(+)/CD8(+) lymphocytes was similar in both groups. The mean concentrations of sIL-2R in NPG (P = 0.011) and POAG (P = 0.0023) patients were higher than that found in control subjects although IL-2 concentrations were similar in these groups. In addition, the reactive ability of T lymphocytes to the non-specific reagent (PHA) was reduced significantly in NPG (P = 0.02) and POAG patients (P=0.04). CONCLUSION: The alterations of the cellular immune system in patients with glaucoma support our hypothesis that the immune system may play an important role in the initiation and/or sustainment of glaucomatous optic neuropathy in some patients.     

Prevalence of migraine in low-tension glaucoma and primary open-angle glaucoma in Japanese.

We studied the prevalence of migraine in low-tension glaucoma (LTG) and primary open-angle glaucoma (POAG). Seventy seven Japanese patients with LTG, 73 with POAG, and 75 normal subjects were randomly selected and tested with a headache questionnaire. The prevalence of headache with or without typical migrainous features (unilateral headache or ocular pain, nausea, vomiting, and visual disturbance before headache) was 51% in LTG, 42% in POAG, and 44% in normal patients. The prevalence of headache with two migrainous features or more (probable migraine) was 17% in LTG, 11% in POAG, and 12% in normal subjects. The prevalence of headache with three migrainous features (classical migraine) was 5% in LTG, 3% in POAG, and 3% in normal subjects. There was no statistically significant difference in the prevalence of any types of migraine between the three groups of patients (p greater than 0.05). These results suggest there is no significant relationship between migraine and LTG or POAG in Japanese patients.