RESUMEN
BACKGROUND: Glaucoma is the irreversible vision loss and contributes second leading cause of blindness worldwide. Matrix metalloproteinase-9 (MMP-9) is involved with remodeling and destruction of extracellular matrix. Elevated MMP-9 levels and various functional variants of MMP-9 have been associated with glaucoma in different population. In the current investigation, we tested association of MMP-9 common variants with different clinical categories of glaucoma in Chinese population. MATERIALS AND METHODS: We enrolled total of 396 glaucoma patients those reported to hospital comprising of 212 primary angle closure glaucoma (PACG) cases and 184 primary open-angle glaucoma POAG patients. In addition, 329 normal individuals from similar geographical areas were enrolled as healthy controls. Five common single nucleotide polymorphisms (rs3918242, rs3918254, rs2250889, rs3918249, and rs17576) were genotyped by PCR-RFLP. Plasma levels of MMP-9 were quantified by ELISA. RESULTS: Heterozygotes (GC) and allele "G" for rs2250889 polymorphism were more frequent in PACG cases compared with healthy controls (GC: P < .0001, OR = 2.26; G: P < .0001, OR = 1.19). Similarly, heterozygous mutant and minor allele for rs3918242 polymorphism were more prevalent in POAG in comparison with healthy controls. Interestingly, distribution of rs17576 variant was statistically higher in both PACG and POAG cases than healthy controls. Furthermore, analysis of plasma MMP-9 with MMP-9 polymorphisms revealed significant association of rs2250889, rs3918242, and rs17576 with plasma levels of the protein. CONCLUSIONS: MMP-9 mutants are associated with elevated plasma MMP-9 and predisposed to development of glaucoma.
Asunto(s)
Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Glaucoma/enzimología , Glaucoma/genética , Hospitales , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Estudios de Casos y Controles , Femenino , Glaucoma/sangre , Glaucoma de Ángulo Cerrado/sangre , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Abierto/sangre , Glaucoma de Ángulo Abierto/enzimología , Glaucoma de Ángulo Abierto/genética , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/sangre , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
PURPOSE: Glaucoma is one of the most important reason causes of the blindness, associated with retinal ganglion cells (RGC) death. This process is not fully understood, however apoptosis due to hypoxia is one of the most important processes leading to RGC death. Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix due to metalloproteinase activation, which leads to loss of RGC and axons at the optic nerve head. The aim of the study was to evaluate metalloproteinase 9 (MMP-9) and tissue metalloproteinase inhibitor-1 (TIMP-1) expression in the retinal ganglion cells and optic nerve axons in 33 eyes with absolute primary glaucoma. MATERIAL/METHODS: To evaluate MMP-9 and TIMP-1 expression primary polyclonal goat antibodies against MMP-9 and TIMP-1 were used. The control group was composed of 8 cases of eyes enucleated and fixed in the first day after trauma. RESULTS: MMP-9 expression was observed in retinal ganglion cells and in the inner nuclear layer of the retina in all the examined cases. In 28 out of 33 glaucomatous eyes, MMP-9 expression was observed in the proliferating glial cells surrounding the optic nerve axons. TIMP-1 expression was observed in 10 out of 33 glaucomatous eyes, only in retinal ganglion cells. None of the examined injured eyes showed MMP-9 and TIMP-1 expression. CONCLUSIONS: MMP-9 activation rather than TIMP-1 may by associated with the pathomechanism of retinal ganglion cell and optic nerve damage in absolute glaucoma.
Asunto(s)
Glaucoma de Ángulo Cerrado/enzimología , Metaloproteinasa 9 de la Matriz/metabolismo , Nervio Óptico/enzimología , Retina/enzimología , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Glaucoma de Ángulo Cerrado/patología , Humanos , Masculino , Persona de Mediana Edad , Disco Óptico/enzimología , Disco Óptico/patología , Nervio Óptico/patología , Retina/patología , Células Ganglionares de la Retina/enzimología , Células Ganglionares de la Retina/patologíaRESUMEN
We investigated whether the c.47T>C polymorphism (SNP rs4880) in the manganese superoxide dismutase (SOD2) gene is a risk factor for primary angle closure glaucoma (PACG) in the Saudi population. Among cases (n=139), the prevalence of various genotypes were 25.9%, 46.8% and 27.3% for T/T, C/T and C/C genotypes respectively. This trend was similar in the controls (n=403); 22.6%, 50.1% and 27.3% for T/T, C/T and C/C respectively. The differences in genotype distribution were not statistically significant (p=0.391 and 0.682 respectively). The minor allele frequency was 50.7% in cases and 52.4% in controls; this difference was not statistically significant (p=0.676). Investigating the potential association between this SOD2 polymorphism and different clinical indices, there was a statistically significant difference among different genotype groups in terms of three important clinical indices for PACG; Mean age at onset, duration of onset to and the mean LogMAR visual acuity (p=0.041, 0.018 and 0.033 respectively). The three markers are highly associated prognostic factors to diseases severity. If our results are proven in larger cohort and in various populations, then this SNP may have potentiality to be used as an indicator for PACG severity.
Asunto(s)
Glaucoma de Ángulo Cerrado/genética , Polimorfismo de Nucleótido Simple , Superóxido Dismutasa/genética , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Glaucoma de Ángulo Cerrado/enzimología , Gonioscopía , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Mutación , Factores de Riesgo , Tonometría OcularRESUMEN
PURPOSE: Matrix metalloproteinases (MMPs) play an important role in remodeling of the extracellular matrix during development and growth of various tissues including the eye. Various functional polymorphisms in MMPs have been implicated in the pathogenesis of different types of glaucoma. The aim of the present study was to investigate the role of various polymorphisms in Pakistani patients with glaucoma. METHODS: The present case-control study included 112 patients with primary open-angle glaucoma (POAG), 82 patients with primary angle closure glaucoma (PACG), and 118 control subjects. Genotyping of polymorphisms was done using PCR followed by restriction fragment length polymorphism analysis. RESULTS: A significant difference in the genotype frequencies of MMP1 rs1799750 (-1607 1G/2G) was observed between the patients with POAG and the control subjects (p = 0.001). This was attributed to the female subjects (p < 0.001), while the association was not significant in male subjects (p > 0.47). In addition, a significant difference was observed in genotype frequencies of MMP9 rs17576 (c.836A>G) in patients with PACG compared to the control subjects (p < 0.001), which after gender stratification remained significant in men (p = 0.009) but not in women (p = 0.14). No significant associations were found for MMP7 (c.-181T>C) and MMP9 (c.-1562C>T) polymorphisms. CONCLUSIONS: Our data suggest that the MMP1 rs1799750 (-1607 1G/2G) and MMP9 rs17576 polymorphisms might be of value for further study as potential gender-dependent risk factors for developing POAG and PACG, respectively, in Pakistan.
Asunto(s)
Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Abierto/enzimología , Glaucoma de Ángulo Abierto/genética , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo Genético , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pakistán , Factores de RiesgoRESUMEN
PURPOSE: To investigate the involvement of stress-regulating genes, endothelial nitric oxide synthase (eNOS) and heat shock protein 70 (HSP70) with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: POAG and PCAG patients recruited from different areas of Pakistan were diagnosed on the basis of clinical history, raised intraocular pressure (IOP), cup-to-disc ratio (CDR) and visual field defects. Their blood was collected and genomic DNA was extracted from it, followed by PCR amplification and VNTR typing of the eNOS gene, while the HSP70 SNP was analyzed with PCR-RFLP. For both of the polymorphisms, the genotype distribution of the POAG and PCAG patients was compared with unaffected controls. RESULTS: HSP70 polymorphism was found to be significantly associated with PCAG (chi(2)=15.29 [p<0.001], OR=2.63 [95% CI=1.55-4.48]), with p<0.001 for the dominant model and OR=2.09 (95% CI=1.10-3.96) , with p<0.01 for the recessive model, but not with POAG (chi(2)=2.96 [p>0.05]). As opposed to this significant eNOS association, was seen with PCAG (chi(2)=6.33 [p<0.05], OR=2.09 [95% CI=1.12-3.89]), with p<0.01 for the dominant model, as well as with POAG (chi(2)=8.89 [p<0.05], OR=2.23 [95% CI=1.26-3.39]), with p<0.01 for dominant model. For the eNOS case, we found a significant association with the risk allele "a" for POAG patients (chi(2)=9.29 [p<0.01], OR=2.02 [95% CI=1.25-3.28, p=0.001]) and PCAG patients (chi(2)=7.59 [p<0.01], OR=1.99 [95% CI=1.18-3.37, p<0.01]). Similarly, in the HSP70 case, there was a significant association with the risk allele "C" for POAG patients (chi(2)=3.57 [p=0.05], OR=1.38 [95% CI=0.97-1.94, p<0.05]) and PCAG patients (chi(2)=18.32 (p<0.001), OR=2.16 [95% CI=1.49-3.13, p<0.001]). CONCLUSIONS: The intron 4 polymorphism of eNOS is associated with POAG, as well as PCAG, while the G+190C polymorphism in HSP70 is associated with PCAG, but not with POAG in the Pakistani population.
Asunto(s)
Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Abierto/genética , Proteínas HSP70 de Choque Térmico/genética , Óxido Nítrico Sintasa de Tipo III/genética , Polimorfismo de Nucleótido Simple/genética , Emparejamiento Base/genética , Estudios de Casos y Controles , Estudios de Cohortes , Frecuencia de los Genes/genética , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Abierto/enzimología , Humanos , Intrones/genética , Repeticiones de Minisatélite/genética , Pakistán , Reacción en Cadena de la PolimerasaRESUMEN
PURPOSE: To investigate the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C genotypes and plasma concentrations of total homocysteine (tHcy) in Pakistani patients with primary open angle glaucoma (POAG) and primary closed angle glaucoma (PCAG). METHODS: This was a prospective case-control study. A total of 295 patients (173 POAG, 122 PCAG) and 143 age- and sex-matched controls were subdivided into two ethnic groups, Punjabis (Punjab province, central Pakistan) and Pathans (North-West Frontier Province, northern Pakistan). Genotypes of the MTHFR C677T and A1298C polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An enzyme-linked immunosorbent assay was used to determine the total serum homocysteine (tHcy) levels. Associations were determined by logistic regression analysis. RESULTS: Frequency distributions of genotypes and combined genotypes as well as homocysteine levels were obtained. The overall distribution of the C677T genotype was found to be significantly associated with PCAG (CC 69%, CT 21%, TT 10%; p=0.001, chi(2)=12.6), but not with POAG (CC 71%, CT 28%, TT 1%; p=0.98, chi(2)=0.02) as compared to the controls (CC 71%, CT 29%, TT 1%). The Pathan cohorts revealed no association with the disease; however, the Punjabis demonstrated a significant association with PCAG (CC 75%, CT 11%, TT 13%; p<0.001, chi(2)=17.2). PCAG in the Punjabi subjects was also significantly associated with the A1298C polymorphism (AA 43%, AC 54%, CC 3%; p<0.001, chi(2)=33.9) as compared to the controls. Combined genotype data showed no association with POAG; however, a significant association with all combined genotypes was observed in the overall PCAG subjects (p<0.05, chi(2)=20.1). This difference was particularly apparent in the TTAA and TTAC combinations that were completely absent in the control groups (p<0.05. chi(2)=49.6). Mean serum tHcy levels were found to be significantly increased in the POAG (15.2+/-1.28 micromol/l, p<0.001) and PCAG (20.8+/-4.8 micromol/l) groups as compared to the controls (10.0+/-0.97 micromol/l). The tHcy levels in the TT and AC genotype were significantly elevated in the PCAG group (67+/-12.39 micromol/l, p<0.001; 23+/-5.94 micromol/l, p=0.027) as compared to the controls. CONCLUSION: The TT and AC genotypes of MTHFR C677T and A1298C polymorphisms and the combined genotype TTAC were associated with PCAG in Punjabi subjects of Pakistani origin and correlated with the high serum tHcy levels seen in these patients.
Asunto(s)
Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Abierto/enzimología , Glaucoma de Ángulo Abierto/genética , Homocisteína/sangre , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Glaucoma de Ángulo Cerrado/sangre , Glaucoma de Ángulo Abierto/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To study the association of the single nucleotide polymorphisms (SNPs) rs17576 and rs2250889 in the extracellular matrix metalloprotease-9 (MMP-9) gene with primary angle closure glaucoma (PACG) in southern Chinese patients. METHODS: DNA samples were obtained from 211 adult patients with PACG and 205 control subjects to study the relationships between SNPs in MMP-9 and PACG. Polymorphism analyses of rs17576 and rs2250889 in MMP-9 were performed using the polymerase chain reaction,restriction fragment length polymorphism (RFLP), and direct DNA sequencing techniques. The association between genetic polymorphisms and the risk of PACG were estimated by chi2 test and logistic regression. RESULTS: Genotyping of the MMP-9 site (rs2250889) was significantly different between the two groups (P=0.004), and the odds ratio was OR=1.76 (95%CI: 1.264-2.449). The frequencies of the G/G genotype in the PACG and control groups were 9% and 2.9%, respectively. However, there were no significant differences between these two groups in the frequencies of the genotypes and alleles for rs17576 in MMP-9. CONCLUSION: The SNP rs2250889 located in MMP-9 might be associated with PACG among southern Chinese people, and people with the G/G genotype are likely more susceptible to PACG. In contrast, the SNP rs17576 in MMP-9 might not be related to PACG in the same population.
Asunto(s)
Pueblo Asiatico/genética , Matriz Extracelular/enzimología , Predisposición Genética a la Enfermedad , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/genética , Metaloproteinasa 9 de la Matriz/genética , Polimorfismo de Nucleótido Simple/genética , Anciano , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Análisis de Secuencia de ADNRESUMEN
PURPOSE: To investigate the differences in the histopathology and matrix metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non-glaucomatous patients. METHODS: POAG and PACG patients, who underwent a trabeculectomy and had no history of ocular disease except glaucoma, were enrolled. The number and instillation period of topical eye drops were reviewed. For the controls, which were patients without glaucoma or a history of ocular surgery, the Tenon's tissue was obtained in the course of retinal detachment surgery. For glaucoma patients, the Tenon's tissue was obtained during the trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti-glaucoma medication and the mean number of anti-glaucoma medications were similar in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG and PACG groups compared to the control group (p=0.03, 0.01, respectively). Compared with the control group, the MMP-2 level was higher in the POAG patients (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels of MMP-9 in the POAG and PACG patients were not significantly different from that of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The MMP expression was altered in the Tenon's tissue of glaucoma patients compared to the control group. The levels of MMP-2 were lower in the PACG patients than in the POAG patients. These results suggest that there may be histopathological differences in the Tenon's tissue of POAG and PACG patients.
Asunto(s)
Tejido Conectivo/enzimología , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Abierto/enzimología , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Adulto , Anciano , Glaucoma de Ángulo Cerrado/cirugía , Glaucoma de Ángulo Abierto/cirugía , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , TrabeculectomíaRESUMEN
BACKGROUND: To study the role of choroidal and retinal vessels in the pathology of secondary angle-closure glaucoma. METHODS: DBA/2NNia and non-glaucomatous C57BL/6J mice over the age range 2-20 months were investigated. Corrosion cast preparations of the vasculature were studied using scanning electron microscopy. Whole mounts of the retina and choroid were stained enzyme-histochemically for NADPH diaphorase as an indicator for nitric oxide synthase activity. Semi- and ultra-thin sections of the posterior eye segment were performed and evaluated. RESULTS: DBA/2NNia mice showed loss of choroidal pigmentation and a decrease in choriocapillary density already at 4 months of age. In animals 9 months and older, a decrease of choroidal NADPH-diaphorase positive nerve fibers was evident. The retinal vasculature showed only mild changes in NADPH-diaphorase staining, even in the oldest animals. The ultrastructural appearance of the retinal vessels was similar in both mouse strains and for all ages investigated. CONCLUSIONS: Choroidal changes in the DBA/2NNia mouse are similar to that seen in other glaucoma models. The lack of retinal vasculature changes in adult and senescent DBA/2NNia mice suggests a normal blood supply of the retina during the progress of secondary angle-closure glaucoma in these animals.
Asunto(s)
Coroides/irrigación sanguínea , Glaucoma de Ángulo Cerrado/fisiopatología , Vasos Retinianos/fisiología , Animales , Capilares/ultraestructura , Coroides/enzimología , Coroides/ultraestructura , Molde por Corrosión , Modelos Animales de Enfermedad , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/etiología , Enfermedades del Iris/complicaciones , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Microscopía Electrónica de Rastreo , NADPH Deshidrogenasa/metabolismo , Fibras Nerviosas/enzimología , Óxido Nítrico Sintasa de Tipo I/metabolismo , Vasos Retinianos/ultraestructuraRESUMEN
PURPOSE: To determine the transcripts expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in Tenon capsule of patients with primary glaucoma and non-glaucomatous patients who serve as the control. PATIENTS AND METHODS: Specimens of Tenon capsule were obtained intraoperatively and evaluated with the reverse transcriptase-polymerase chain reaction method. The transcripts levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 relative to that of glyceraldehyde phosphate dehydrogenase were determined. RESULTS: The transcripts levels of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were not correlated with age in the control group. There were differences in the transcripts expression of MMP-2 (P < 0.001), MMP-9 (P = 0.017), TIMP-1 (P < 0.001), and TIMP-2 (P = 0.001) among the control, primary open angle glaucoma, and primary angle-closure glaucoma groups (Kruscal-Wallis H test). Comparing with the controls, open angle glaucoma had decreased transcripts levels of MMP-2 (P = 0.001) and TIMP-1 (P = 0.006) while angle-closure glaucoma had decreased transcripts levels of MMP-2 (P < 0.001), MMP-9 (P = 0.004), TIMP-1 (P < 0.001), and TIMP-2 (P < 0.001) (Mann-Whitney U tests). CONCLUSION: The transcripts expression of certain MMPs and TIMPs is altered in Tenon capsule of glaucoma patients, which might result from long-term application of topical glaucoma medications.
Asunto(s)
Tejido Conectivo/metabolismo , Ojo/metabolismo , Glaucoma/metabolismo , Metaloproteinasas de la Matriz/genética , ARN Mensajero/metabolismo , Inhibidores Tisulares de Metaloproteinasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Tejido Conectivo/enzimología , Ojo/enzimología , Femenino , Glaucoma/enzimología , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/metabolismo , Glaucoma de Ángulo Abierto/enzimología , Glaucoma de Ángulo Abierto/metabolismo , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
PURPOSE: To characterize retinal amacrine cell changes in eyes of DBA/2NNia (DBA) mice that develop an inherited angle-closure glaucoma. METHODS: DBA and non-glaucomatous C57BL/6J mice of different age groups (2 to 23 months of age) were studied and compared. Morphologic investigations included NADPH-diaphorase staining of retinal whole mounts and fluorescence immunohistochemistry of cryosections with antibodies against neuronal nitric oxide synthase (nNOS), tyrosin hydroxylase (TH), gamma aminobutyric acid (GABA), and vesicular acetylcholine transporter (VAChT). RESULTS: Immunohistochemistry of amacrine cell subpopulations in the retinae of DBA mice revealed no significant staining differences in the two mouse strains at all ages using antibodies against TH, GABA, and VAChT. However, staining with nNOS and NADPH diaphorase revealed significant differences between the DBA strain and the C57BL/6J mice. With the onset of elevated IOP and glaucoma beginning at around 6 months in the DBA mice, the total number of NOS positive amacrine cells continuously decreased from 1000 cells at 6 months of age down to 480 cells in animals older than 20 months of age, but did not decline in age-matched C57 mouse retinas. CONCLUSION: We previously described a parafoveal loss of nNOS positive amacrine cells in the monkey glaucoma model. The fact that there is also a significant decrease of nNOS amacrine cells in the glaucomatous mouse eye indicates a specific response of nNOS positive amacrine cells in glaucomatous retinopathy.
Asunto(s)
Células Amacrinas/enzimología , Modelos Animales de Enfermedad , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Cerrado/genética , Ratones Endogámicos DBA/genética , Óxido Nítrico Sintasa/metabolismo , Retina/enzimología , Células Amacrinas/metabolismo , Animales , Glaucoma de Ángulo Cerrado/metabolismo , Glaucoma de Ángulo Cerrado/patología , Inmunohistoquímica , Proteínas de Transporte de Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , NADPH Deshidrogenasa/metabolismo , Óxido Nítrico Sintasa de Tipo I , Retina/metabolismo , Retina/patología , Tirosina 3-Monooxigenasa/metabolismo , Proteínas de Transporte Vesicular de Acetilcolina , Ácido gamma-Aminobutírico/metabolismoRESUMEN
PURPOSE: Primary open-angle glaucoma (POAG) is the predominant form of chronic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a change in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. METHODS: Expression of COX-1 and -2 was assessed by confocal laser microscopy, immunohistochemistry, Western blot analysis, and real-time RT-PCR in human eyes with different forms of glaucoma (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous humor by means of an enzyme-linked immunoassay as a product of COX activity. RESULTS: In normal eyes, ocular COX-1 and -2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body. By immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end-stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma and was reduced in patients receiving topical steroid treatment. Eyes of patients with either congenital juvenile or angle-closure glaucoma showed COX-2 expression indistinguishable from control eyes. Aqueous humor of eyes with POAG contained significantly less PGE2 than control eyes. CONCLUSIONS: Both cyclooxygenase isoforms are constitutively expressed in the normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurrence of POAG and steroid-induced glaucoma.
Asunto(s)
Cuerpo Ciliar/enzimología , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Abierto/enzimología , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Humor Acuoso/metabolismo , Western Blotting , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Dinoprostona/metabolismo , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/enzimología , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Isoenzimas/genética , Proteínas de la Membrana , Microscopía Confocal , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Prostaglandina-Endoperóxido Sintasas/genética , ARN/aislamiento & purificación , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: To investigate whether abnormal expression of gelatinase A in aqueous humor may be related to the development of glaucoma, the activity of gelatinase A in aqueous humor of patients with glaucoma and patients with cataract was measured and compared. METHODS: Six primary patients with open-angle glaucoma (POAG), four patients with chronic angle closure glaucoma (CACG), four patients with normal tension glaucoma (NTG), and 14 patients with cataract were enrolled. The aqueous humor of each patient was collected during surgery, and total protein concentration and gelatinase activity in the aqueous humor were measured by protein assay kit and zymography, respectively. RESULTS: In patients with POAG, total protein concentration doubled and gelatinase A activity increased by 3.9 times compared with patients with cataract. However, there were no statistically significant differences in total protein concentration and gelatinase A activity in patients with CACG or NTG compared with patients with cataract. CONCLUSION: The development of POAG may be associated with the abnormal expression of gelatinase A in aqueous humor.
Asunto(s)
Humor Acuoso/enzimología , Gelatinasas/metabolismo , Glaucoma de Ángulo Cerrado/enzimología , Glaucoma de Ángulo Abierto/enzimología , Metaloendopeptidasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Catarata/enzimología , Enfermedad Crónica , Densitometría , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Presión Intraocular , Masculino , Metaloproteinasa 2 de la Matriz , Persona de Mediana Edad , PronósticoRESUMEN
Ocular drainage zone tissue, obtained during surgery from patients with glaucoma, was examined. Chemiluminescence has revealed changed amplitude of the flash and the value of its total light volume. Increased intensity of peroxide chemiluminescence evidences enhanced processes of lipid peroxidation in the tissue and a reduced antioxidant level. Histochemical study of acid phosphatase has discovered destabilization of lysosomal membranes, more marked during an acute attack of glaucoma.