Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome / Avaliação dos níveis de renina e angiotensina II na síndrome de pseudo-exfoliação

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.

RESUMO Objetivo: A síndrome de pseudo-exfoliação tem sido associada ao comprometimento da função do coração e dos vasos sanguíneos. Foi realizado um estudo para investigar o papel do sistema renina-angiotensina na etiopatogenia da síndrome de pseudo-exfoliação. Métodos: Os sujeitos foram 14 pacientes com síndrome de pseudo-exfoliação e 14 controles saudáveis submetidos à extração de catarata. Amostras pré-operatórias de 5 ml de sangue venoso periférico e humor aquoso perioperatório foram coletadas dos pacientes em ambos os grupos. Os níveis de renina no plasma e humor aquoso foram analisados pelo método imunorradiométrico e os níveis de angiotensina II foram analisados por radioimunoensaio. O SPSS versão 16.0 foi utilizado para análises estatísticas. Considerou-se o valor de p<0,05 para indicar uma diferença estatisticamente significativa. Resultados: A média de idade dos pacientes nos grupos pseudo-exfoliação e controle foi de 71,7 ± 7,1 e 67,4 ± 9,3 anos, respectivamente (p=0,140). O nível médio de renina no humor aquoso foi de 7,73 pg / ml (4,15-21) no grupo controle e 11,95 pg/ml (3,75-18,54) no grupo pseudo-exfoliação (p=0,022). Não houve diferenças entre os dois grupos de renina plasmática, angiotensina II plasmática ou nos níveis de angiotensina II em humor aquoso. As correlações entre os níveis de renina no plasma e no humor aquoso e entre os níveis de angiotensina II no plasma e humor foram examinadas separadamente para cada grupo; n]ao foram observadas correlações significativas no grupo pseudo-exfoliação (r=-0,440, p=0,115; r=-0,414, p=0,142) ou no grupo controle (r=-0,232, p=0,425; r=0,482, p=0,081). Conclusão: Os níveis de renina no humor aquoso são mais elevados na síndrome de pseudo-exfoliação. Os resultados indicam um provável papel do sistema renina-angiotensina na síndrome de pseudo-exfoliação. Novos estudos com maior número de casos são necessários para esclarecer a associação precisa do sistema renina-angiotensina com a etiopatogenia da síndrome de pseudo-exfoliação.

Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome / Mutações no gene da cadeia leve da ferritina em duas famílias brasileiras com síndrome hereditária hiperferritinemia-catarata

ABSTRACT Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5'UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5'UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.

RESUMO A síndrome hereditária hiperferritinemia-catarata é uma doença genética autossômica dominante associada a mutações na região 5'UTR do gene da cadeia leve da ferritina. Estas mutações elevam os níveis de ferritina, mesmo na ausência de sobrecarga de ferro. Os pacientes também desenvolvem catarata bilateral precocemente, devido ao acúmulo de ferritina no cristalino, e muitos são erroneamente diagnosticados como portadores de hemocromatose, sendo tratados de maneira inadequada. Os primeiros casos foram descritos em 1995, e diversas mutações já foram identificadas. Entretanto, essa síndrome ainda é pouco conhecida. Relatamos dois casos de famílias brasileiras, não relacionadas, com suspeita clínica da síndrome, que foram atendidas em nosso serviço. Para o diagnóstico definitivo, os pacientes afetados, seus pais e irmãos foram submetidos à pesquisa de mutação do gene ferritina, por sequenciamento de Sanger da região 5'UTR. Foram encontradas mutações do tipo polimorfismo de nucleotídeo único nos pacientes afetados, já descritas anteriormente. O teste auxiliou no diagnóstico preciso da doença e é importante ser divulgado, para ser incorporado na prática clínica.

Comparative Quantification of Plasma TDRD7 mRNA in Cataract Patients by Real-time Polymerase Chain Reaction

PURPOSE: To investigate the relationship between plasma TDRD7 mRNA and lens transparency, and to evaluate plasma TDRD7 mRNA as a potential marker for cataracts and its sub-type by quantitatively analyzing human peripheral blood. METHODS: Plasma RNA was extracted from 40 patients with cataracts, and 30 normal controls of matched age and gender. Blood cholesterol and fasting glucose were measured, and the RNA extracted from the sample was synthesized into cDNA. After polymerase chain reaction, the results were compared after quantifying the TDRD7 mRNA using ABL1 mRNA for normalization. We analyzed the relative gene expression data via the DeltaDeltaCt method. RESULTS: The normalized 2(-DeltaDeltaCt) of plasma TDRD7 mRNA based on ABL1 mRNA was 1.52 ± 0.63 in the case of the control group and 1.05 ± 0.34 in the case of the cataract patients, and the TDRD7 expression level of the cataract patients was lower than that of the control group (p = 0.048). The comparison of the genetic values of different types of cataracts demonstrated that the TDRD7 expression level of the cortical type and mixed type were lower than those of the nuclear type and posterior subcapsular opacity type (p = 0.017). CONCLUSIONS: Human cataracts and the TDRD7 gene loss-of-function mutations are strongly causally related, as the expression level of plasma TDRD7 mRNA in patients with cataracts was statistically significantly lower than in the normal control group.

Correlation of cataract with serum lipids, glucose and antioxidant activities a case-control study / Correlación de la Catarata con los Lípidos Séricos, la Glucosa, y las Actividades Antioxidante Un Estudio de Caso-control

OBJECTIVE: The aim of this study is to evaluate the relationship between cataract development and serum lipids, glucose as well as antioxidants in a case-control study. METHODS: Ninety patients with cataract and 90 age- and sex-matched healthy controls were investigated. Lipid profiles including triglyceride (Tg), total serum cholesterol (Chol) and cholesterol content in high-density lipoproteins (HDL chol) and low-density lipoproteins (LDL chol) as well as fasting glucose (FBS) were measured for all subjects. Plasma oxidative stress as thiobarbituric acid-reactive substances (TBARS) and the status of antioxidants were studied as ferric reducing/antioxidant power (FRAP) and thiol substance assay. RESULTS: A higher prevalence of abnormal FBS (8.9 vs 1.1%), Tg (26.7 vs 8.9%) and Chol (54.4 vs 30%) was found in cataract patients than the control group (p <0.05). Plasma Tg (p = 0.02), Chol (p = 0.001) and LDL chol (p = 0.04) were significantly higher in the cataract group than in the control group. Likewise TBARS (p = 0.05) as the level of oxidative stress was significantly higher in the case group, and FRAP (p = 0.03) and thiol (p = 0.02) assays as the antioxidant activity was significantly lower among cataract patients. CONCLUSION: This study has shown that hypercholesterolaemia, hypertriglyceridaemia, high LDL chol and high FBS are associated with cataract. Also lower plasma antioxidant levels and higher levels of oxidative stress were seen in cataract patients than healthy controls. These findings indicate a need for health promotional activities aimed at controlling these preventable factors among high risk populations.

OBJETIVO: El objetivo de este estudio es evaluar la relación entre el desarrollo de la catarata y los lípidos séricos, la glucosa, así como los antioxidantes, en un estudio de caso-control. MÉTODOS: Se investigaron noventa pacientes y noventa controles sanos, pareados por edady sexo. Los perfiles lípidos, incluyendo los triglicéridos (Tg), el colesterol sérico total (Chol) y el contenido de colesterol en lipoproteínas de alta densidad (HDL chol) y lipoproteínas de baja densidad (LDL chol) fueron medidos en todos los sujetos, así como la glucosa en ayunas (FBS). Se estudió el estrés oxidativo en plasma como sustancias reactivas al ácido tiobarbitúrico (TBARS) y el estado de los antioxidantes comopoder reductor férrico/antioxidante (FRAP) y ensayo de tiol. RESULTADOS: Se encontró unaprevalencia mayor de FBS anormal (8.9 vs. 1.1%), Tg (26.7 vs 8.9%) y Chol (54.4 vs 30%) en los pacientes con catarata, en comparación con el grupo control (p <0.05). El Tg en plasma (p = 0.02), Chol (p = 0.001) y LDL chol (p = 0.04) fueron significativamente más altos en el grupo con catarata que en el grupo control. Igualmente TBARS (p = 0.05) como nivel de estrés oxidativo fue significativamente más alto en el grupo de caso, y FRAP (p = 0.03) y el ensayo de tiol (p = 0.02) como actividad antioxidante fue significativamente más baja entre los pacientes con catarata. CONCLUSIÓN: Este estudio mostró que la hipercolesterolemia, la hipertrigliceridemia, el colesterol LDL alto, y el FBS alto se hallan asociados con la catarata. También se observaron niveles más bajos de antioxidante plasmático y niveles más altos de estrés oxidativo en los pacientes con cataratas frente a los controles saludables. Estos hallazgos indican una necesidad de actividades de promoción de la salud afin de controlar estos factores prevenibles entre la población de alto riesgo.

Total antioxidant capacity in Eales’ disease, uveitis & cataract.

Background & objectives: The human system possesses antioxidants that act harmoniously to neutralize the harmful oxidants. This study was aimed to evaluate the serum total antioxidant capacity (TAC) as a single parameter in Eales’ disease (ED) and in an acute inflammatory condition such as uveitis and in cataract which is chronic, compared to healthy controls. Methods: The TAC assay was done spectrophotometrically in the serum of Eales’ disease cases (n=20) as well as in other ocular pathologies involving oxidative stress namely, uveitis and cataract (n=20 each). The oxidative stress measured in terms of TBARS, was correlated with the TAC. Individual antioxidants namely vitamin C, E and glutathione were also estimated and correlated with TAC. Results: TAC was found to be significantly lower in Eales’ disease with active vasculitis (0.28 ± 0.09 mM, P<0.001), Eales’ disease with healed vasculitis (0.67 ± 0.09 mM), uveitis (0.46 ± 0.09 mM, P<0.001) and cataract (0.53 ± 0.1 mM, P=0.001) compared to the healthy controls, with a TAC level of 0.77 ± 0.09 mM. The TAC was found to correlate positively with vitamin E levels (P=0.05), GSH (P=0.02) but not with vitamin C, as seen in ED cases. In ED cases supplemented with vitamin E and C, there was a significant increase in the TAC level (P=0.02). Interpretation & conclusions: The TAC measurement provided a comprehensive assay for establishing a link between the antioxidant capacity and the risk of disease as well as monitoring antioxidant therapy. This method is a good substitute for assay of individual antioxidants as it clearly gives the status of the oxidative stress in the disease process.

Concentrações plasmáticas e eritrocitárias de zinco em idosos portadores e não-portadores de catarata senil em um serviço oftalmológico especializado de Teresina-Piauí / Plasma and erythrocyte zinc concentrations in elderly patients with and without senile cataract in a tertiary eye care center at Teresina-Piauí

OBJETIVO: Determinar as concentrações plasmáticas e eritrocitárias de zinco em idosos portadores e não-portadores de catarata senil em um serviço oftalmológico especializado, em Teresina-Piauí. MÉTODOS: Estudo quantitativo, transversal e controlado, realizado no Hospital de Olhos Francisco Vilar, Piauí, Brasil. Participaram 56 idosos (37 mulheres, 19 homens) sem condições associadas a modificações nos níveis de zinco ou aumento do risco de catarata. Escore > II foi utilizado para definir a presença de catarata, de acordo com o Lens Opacities Classification System II. As concentrações de zinco foram determinadas por espectrometria de absorção atômica em chama. Análise estatística incluiu os testes t de Student e qui-quadrado e 0,05 como nível de significância. RESULTADOS: Catarata senil foi identificada em 58,9 por cento dos participantes, predominando o tipo nuclear (51,8 por cento), seguido pelo cortical (26,8 por cento) e subcapsular posterior (8,9 por cento). Deficiência de zinco no plasma (<70 μg/dL) e no eritrócito (<40 μg/gHb) foi constatada em 49,1 por cento e 30,4 por cento dos idosos, respectivamente. Não houve diferenças significativas entre portadores e não-portadores de catarata, independente do tipo, quanto às concentrações de zinco plasmático (p=0,165) ou eritrocitário (p=0,426). CONCLUSÃO: Deficiência de zinco no plasma ou eritrócito foi comum entre os idosos; porém, os dados indicam não haver diferenças significativas nos referidos parâmetros quanto à presença de catarata senil, independente do tipo.

PURPOSE: To determine plasma and erythrocyte zinc concentrations in elderly with and without senile cataract in a tertiary eye care center at Teresina-Piauí. METHODS: A quantitative, transversal and controlled study was developed at the Hospital de Olhos Francisco Vilar, Piauí, Brasil. Fifty-six elderly subjects (37 females, 19 males) with no known conditions that modify zinc blood levels or increase risk of cataract were included. A score >II was used to define cataract, according to Lens Opacities Classification System II. Plasma and erythrocyte zinc concentrations were determined by flame atomic absorption spectrometry. Statistical tests included Student's t and chi-square tests, with a probability level of 0.05 as significant. RESULTS: Senile cataract was present in 58.9 percent of the subjects. The most common type was nuclear (51.8 percent), followed by cortical (26.8 percent) and posterior subcapsular (8.9 percent). Zinc deficiencies in plasma (<70 μg/dL) and erythrocyte (<40 μg/gHb) were found in 49.1 percent and 30.4 percent of participants, respectively. There were no significant differences between elderly with or without cataract, regardless of type, in relation to plasma (p=0.165) or erythrocyte (p=0.426) zinc concentrations. CONCLUSION: Zinc deficiency in plasma or erythrocyte were common among the elderly. However, the data suggest that no significant differences exist between elderly with or without senile cataract, regardless of type, in relation to the referred parameters of zinc evaluation.

Changes in erythrocyte glucose-6-phosphate dehydrogenase (G6PD) and reduced glutathione (GSH) activities in the development of senile and diabetic cataracts.

Oxidative and osmotic stress have been implicated in the pathogenesis of cataracts. Reactive oxygen intermediates (ROI) mediate peroxidation of membrane lipids and cause irreversible damage to lens proteins. The purpose of this study was to assess the changes in erythrocyte glucose- 6-phosphate dehydrogenase enzyme (G6PD) and reduced glutathione (GSH) levels in the development of senile and diabetic cataracts. The activity of erythrocyte G6PD and the concentration of GSH were measured to assess changes in oxidation-reduction status. The oxidation-reduction status of 26 non-diabetic non-cataract (control) subjects were compared with 24 diabetic non-cataract, 30 diabetic cataract and 28 non-diabetic cataract subjects. The results revealed that the GSH and G6PD levels of the subjects with senile cataracts were significantly lower than the subjects without cataracts. The present study reveals the risk of developing senile cataracts is associated with decreased levels of erythrocyte G6PD and GSH. In the formation of diabetic cataracts an adequate supply of NADPH (G6PD activity) is essential to produce osmotically active sorbitol in the lens.

Changes in glutathione, glutathione-linked enzymes and hexose monophosphate shunt enzymes in senile cataract.

Changes in glucose-6-phosphate dehydrogenase (G-6-PD), glutathione reductase (GSH-R), reduced glutathione (GSH), glutathione peroxidase (GSH-PO), transketolase (TK) and transaldolase (TA) were studied in lens and red blood cells (RBCs) to understand the possible biochemical mechanisms responsible for the development of senile cataract. The activity of G-6-PD was increased in lens, though not so in erythrocytes during cataractogenesis. A marked decrease was observed in GSH level and GSH-R activity in the lens and RBCs of the cataractous group. The activity of GSH-PO was remarkably high in lens but not in the erythrocytes during the maturity of cataract. The activity of TK decreased gradually in both the lens and erythrocytes. The activity of TA decreased in erythrocytes but increased in the lens with maturation of cataract.