Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration.

PURPOSE: To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. METHODS: Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. RESULTS: A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. CONCLUSIONS: Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration / Níveis circulantes da lectina ligadora de manose (MBL) na degeneração macular relacionada à idade

ABSTRACT Purpose: To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. Methods: Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. Results: A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. Conclusions: Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

RESUMO Objetivos: Avaliar se as concentrações séricas da lectina ligante de manose da via das lectinas do sistema complemento estão associadas à degeneração macular relacionada à idade. Métodos: Pacientes com degeneração macular relacionada à idade a controles pareados realizaram exame oftalmológico completo e imagens de tomografia de coerência óptica. As concentrações de lectina ligante de manose foram aferidas em amostras de sangue pelo método "time-resolved Immunofluorometric assay". Resultados: Um total de 136 indivíduos foram avaliados incluindo 68 com degeneração macular relacionada à idade (34 exsudativa e 34 não-exsudativa) e 68 controles. Concentrações medianas de lectina ligante de ma-nose foram 608 ng/mL (30-3,415 ng/mL) nos casos e 739 ng/mL (30-6,039 ng/mL) nos controles, não havendo diferença entre os grupos. Comparando degeneração macular relacionada a idade exsudativa (mediana de lectina ligante de manose 476 ng/mL; 30-3,415 ng/mL) e não-exsudativa (692 ng/mL; 30-2,587 ng/mL) também não apresentaram diferença. Conclusões: Concentrações séricas de lectina ligante de manose não estão relacionadas à degeneração macular relacionada a idade ou às formas exsudativa e não-exsudativa.

Dynamic thiol/disulfide homeostasis in patients with age-related macular degeneration.

PURPOSE:: We evaluated dynamic thiol/disulfide homeostasis (TDH), malondialdehyde (MDA) levels, and catalase (CAT) activity in patients with age-related macular degeneration (AMD). All analyzes were conducted on plasma samples. METHODS:: Thirty-two patients with AMD and 38 age-matched healthy controls were included. Native thiol, total thiol, and disulfide levels and TDH status were determined using a novel, automated assay. MDA levels and CAT activity were determined. Percentages were compared using the chi-squared test. The Student's t-test and Mann-Whitney U-test were used to compare quantitative variables. RESULTS:: Native thiol levels were significantly lower (p=0.004) in patients with AMD (272.02 ± 52.41 µmol/l) than in healthy individuals (307.82 ± 47.18 µmol/l), whereas disulfide levels were significantly higher (p<0.001) in patients with AMD than in controls (21.64 ± 5.59 vs. 14.48 ± 5.37 µmol/L). Dynamic TDH was also significantly lower (p<0.001) in patients with AMD than in controls (13.41 ± 4.3 vs. 25.41 ± 14.52 µmol/l). No significant differences were evident in total thiol or MDA levels. Mean CAT activity was significantly higher (p=0.043) in patients with AMD compared with controls (0.035 vs. 0.018 k/ml). CONCLUSIONS:: The antioxidant/oxidant balance demonstrated by dynamic TDH is shifted to the oxidative side in patients with AMD.

Dynamic thiol/disulfide homeostasis in patients with age-related macular degeneration / Homeostase dinâmica de tiol/dissulfureto em pacientes com degeneração macular relacionada à idade

ABSTRACT Purpose: We evaluated dynamic thiol/disulfide homeostasis (TDH), malondialdehyde (MDA) levels, and catalase (CAT) activity in patients with age-related macular degeneration (AMD). All analyzes were conducted on plasma samples. Methods: Thirty-two patients with AMD and 38 age-matched healthy controls were included. Native thiol, total thiol, and disulfide levels and TDH status were determined using a novel, automated assay. MDA levels and CAT activity were determined. Percentages were compared using the chi-squared test. The Student's t-test and Mann-Whitney U-test were used to compare quantitative variables. Results: Native thiol levels were significantly lower (p=0.004) in patients with AMD (272.02 ± 52.41 µmol/l) than in healthy individuals (307.82 ± 47.18 µmol/l), whereas disulfide levels were significantly higher (p<0.001) in patients with AMD than in controls (21.64 ± 5.59 vs. 14.48 ± 5.37 µmol/L). Dynamic TDH was also significantly lower (p<0.001) in patients with AMD than in controls (13.41 ± 4.3 vs. 25.41 ± 14.52 µmol/l). No significant differences were evident in total thiol or MDA levels. Mean CAT activity was significantly higher (p=0.043) in patients with AMD compared with controls (0.035 vs. 0.018 k/ml). Conclusions: The antioxidant/oxidant balance demonstrated by dynamic TDH is shifted to the oxidative side in patients with AMD.

RESUMO Objetivo: Avaliar a homeostase dinâmica de tiol/dissulfureto e os níveis de malon dialdeído (MDA) e catalase (CAT) em pacientes com degeneração macular relacionada à idade (DMRI). Todas as análises foram realizadas em amostras de plasma. Métodos: Foram incluídos 32 pacientes com degeneração macular relacionada à idade e 38 controles saudáveis de idade similar. Os níveis de tiol, tiol total, dissulfureto e estado de homeostase de tiol/dissulfureto foram determinados utilizando um novo ensaio automatizado. Os níveis de atividade de MDA e CAT foram também determinados. As porcentagens foram comparadas pelo teste do qui-quadrado. O teste t de Student e o teste U de Mann Whitney foram utilizados para comparar variáveis quantitativas. Resultados: Os níveis de tiol nativo foram significativamente menores (p=0,004) nos pacientes com degeneração macular relacionada à idade (272,02 ± 52,41 µmol/l) do que nos indivíduos saudáveis (307,82 ± 47,18 µmol/l), enquan to os dissulfetos foram significativamente maiores em pacientes com degeneração macular relacionada à idade (21,64 ± 5,59 µmol/l versus 14,48 ± 5,37 µmol/l, respectivamente, p<0,001). A homeostase dinâmica de tiol/dissulfureto também foi significativamente menor nos pacientes com degeneração macular re la cionada à idade (13,41 ± 4,3 µmol/l) versus os controles (versus 25,41 ± 14,52 µmol/l, p<0,001). Não foram observadas diferenças significativas nos níveis de tiol total ou MDA. A atividade média de CAT foi significativamente mais elevada (p=0,043) em doentes com degeneração macular relacionada à idade (0,035 k/ml vs. 0,018 k/ml). Conclusões: O equilíbrio antioxidante/oxidante demonstrado pela homeostase dinâmica de tiol/dissulfeto é deslocado para o lado oxidativo em pacientes com de generação macular relacionada à idade.

Association of high-density lipoprotein and apolipoprotein E genetic variants with age-related macular degeneration.

PURPOSE: This study aimed to evaluate the association of age-related macular degeneration (AMD) with apolipoprotein E (APOE) variants and serum lipid profiles, including levels and fractions of total serum cholesterol (TC), low-density lipoprotein cholesterol (LDLc), and high-density lipoprotein cholesterol (HDLc), and triglycerides (TG). METHODS: Genotyping of APOE-HhaI was performed in 134 patients (study group, SG) and 164 individuals without AMD (control group, CG), aged 50-89 years. Lipid profiles were analyzed in a subgroup of 30 subjects of both groups, matched according to age and sex. The significance level was set at P<0.05. RESULTS: APOE E3/E3 was more prevalent (SG=74.6%; CG=77.4%), with no difference between both groups (P=0.667). The same result was observed for risk genotypes (APOE E -/2: SG=7.4%; CG=10.3%, P=0.624). Serum levels of TC, LDLc, and TG revealed similar median values between SG (193.5, 116, and 155 mg/dL, respectively) and CG (207.5, 120, and 123.5 mg/dL, respectively; P >0.05). For HDLc, a higher median value was observed in SG (53.3 mg/dL) versus CG (42.5 mg/dL; P=0.016). Logistic regression analysis showed the same value, and the HDLc/TC ratio was -11.423 (P=0.014), as also confirmed by an increase in HDLc in SG. The association between lipid profiles and apolipoprotein E genotypes was similar in both groups (P>0.05). CONCLUSION: APOE-HhaI is not associated with AMD. However, an increase in serum HDLc level appears to exert a protective effect against the disease, irrespective of the genetic variants of apoE.

Plasma levels of complement proteins from the alternative pathway in patients with age-related macular degeneration are independent of Complement Factor H Tyr4°²His polymorphism.

PURPOSE: To investigate the influence of the Factor H (CFH) Tyr4°²His polymorphism on the plasma levels of the alternative pathway proteins CFH, C3, Factor B (FB), Factor D (FD), and Factor I (FI) and the inflammatory marker C-reactive protein (CRP) in 119 patients with age-related macular degeneration (AMD) and 152 unrelated control individuals. METHODS: Patients with AMD and the control group were separated according to CFH polymorphism, age, and gender. Plasma complement proteins and CRP concentrations were determined with enzyme-linked immunosorbent assay, immunodiffusion, or nephelometry. RESULTS: Significant differences in the concentrations of FD and FI were observed between the patients with AMD and the control individuals. We observed significantly reduced FD plasma levels in patients with AMD. We also identified a significant decrease in CFH plasma levels in female patients with AMD in relation to female controls. Plasma FI levels were significantly increased in patients with AMD compared to the control group. Regarding gender, a significant increase in FI plasma levels was observed in male patients. Finally, we found no significant correlation between the CFH Tyr(402)His polymorphism and the CFH, C3, FB, FD, FI, and CRP plasma levels. CONCLUSIONS: Patients with AMD present altered levels of FD and FI in a manner independent of this CFH polymorphism, and gender apparently contributes to the plasma levels of these two proteins in patients with AMD and control individuals.