RESUMO
We were intrigued to analyze donor eyes of two individuals without retinopathy even after 40 years of type 2 diabetes mellitus. Targeted molecular factors associated with angiogenesis and the key antioxidant enzymes in retinal tissue were analyzed. Accordingly PEDF, Adiponectin and Paraoxonase 2 showed augmented mRNA expression in both the retina with no significant change in VEGF expression. Vitreous showed increased PEDF protein in donor 1 and Adiponectin in donor 2 with no change in VEGF protein. This study highlights the profile of specific molecular factors that contribute to the non-development of diabetic retinopathy changes in these individuals.
Assuntos
Adiponectina/biossíntese , Arildialquilfosfatase/biossíntese , Diabetes Mellitus Tipo 2/diagnóstico , Proteínas do Olho/biossíntese , Regulação da Expressão Gênica , Fatores de Crescimento Neural/biossíntese , Retina/patologia , Serpinas/biossíntese , Doadores de Tecidos , Adiponectina/genética , Idoso de 80 Anos ou mais , Arildialquilfosfatase/genética , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Proteínas do Olho/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/genética , Estresse Oxidativo , RNA/genética , Retina/metabolismo , Doenças Retinianas , Serpinas/genéticaRESUMO
BACKGROUND & OBJECTIVES: Age related macular degeneration (ARMD) is a leading cause of blindness, particularly in persons above 60 yr of age. Homocysteine is implicated in many ocular diseases including ARMD. This study was undertaken to assess the status and relationship between plasma homocysteine, homocysteine - thiolactone, homocysteinylated protein and copper levels in patients with ARMD. METHODS: A total of 16 patients with ARMD and 16 age-matched controls were recruited for the study. Plasma glutathione, homocysteine, homocysteine - thiolactone and extent of homocysteine conjugation with proteins, copper and thiobarbituric acid reactive substances were measured. RESULTS: Homocysteine levels were elevated with increase in homocysteine-thiolactone, thiobarbituric acid reactive substances and a decrease of glutathione. The levels of homocysteinylated protein were elevated in ARMD. The elevated homocysteine, homocysteine-thiolactone correlated with the decrease in copper level. INTERPRETATION & CONCLUSIONS: Elevated homocysteine and its metabolite homocysteine-thiolactone and decreased levels of copper may play an important role in the pathogenesis of ARMD.
Assuntos
Cobre/sangue , Homocisteína/análogos & derivados , Homocisteína/sangue , Degeneração Macular/sangue , Idoso , Cobre/deficiência , Feminino , Glutationa/sangue , Humanos , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
PURPOSE: Lysyl oxidase (LOX) cross-links the side chain of collagen and elastin and thereby contributes to extracellular matrix (ECM) integrity. ECM remodeling is seen in various ocular diseases. Until now, there have been no reports on the LOX enzyme's activity in ocular tissues. The purpose of this study was to estimate LOX activity and expression in human donor ocular tissues and to measure the specific activity of LOX in the vitreous of proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD). METHOD: Human donor eyeballs obtained from an eye bank were used to study tissue distribution of LOX. Human vitreous specimens were obtained during vitreoretinal surgery from PDR (n = 16) and RRD (n = 10). LOX activity was estimated by N-acetyl-3,7-dihydroxyphenoxazine assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR). Matrix metalloprotease (MMP)-2 and -9 were quantified in the vitreous by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The specific activity of LOX in ocular tissues was on the order of vitreous, iris ciliary body, lens, choroid RPE, and retina, which were comparable by mRNA expression and immunolocalization. The vitreous level of LOX activity decreased significantly in PDR and RRD, with an increase in total MMP-2 and -9 levels compared with normal donor vitreous. CONCLUSIONS: LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases.
Assuntos
Retinopatia Diabética/enzimologia , Expressão Gênica , Proteína-Lisina 6-Oxidase/genética , RNA/genética , Descolamento Retiniano/enzimologia , Vitreorretinopatia Proliferativa/enzimologia , Idoso , Corioide/enzimologia , Corpo Ciliar/enzimologia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Cristalino/enzimologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Reação em Cadeia da Polimerase , Proteína-Lisina 6-Oxidase/biossíntese , Retina/enzimologia , Descolamento Retiniano/genética , Descolamento Retiniano/patologia , Vitreorretinopatia Proliferativa/genética , Vitreorretinopatia Proliferativa/patologia , Corpo Vítreo/enzimologiaRESUMO
Eales disease was shown to be associated with oxidant stress and weak antioxidant defense. Total iron, ferrous iron, thiobarbituric acid reactive substances (TBARS), and ceruloplasmin were estimated in the blood samples of patients with inflammation, perivasculitis, and venous insufficiency. Levels of ferric iron were determined from the difference in those of total iron and ferrous iron. All biochemical parameters were estimated in age and sex-matched controls. Fe3+/Fe2+ ratio was greater in patients with Eales disease than in normal controls. Similar increase in TBARS and ceruloplasmin levels were noted. The patients were treated with prednisone and vitamins E and C, then Fe3+/Fe2+ ratios and TBARS decreased progressively; the active state of the disease was reduced to 16%. So Fe3+/Fe2+ ratio in addition to TBARS levels could be considered an index of the active state of the disease. Circulating transferrin in blood did contain ferrous iron. Binding of ferrous iron to transferrin was confirmed by estimating iron-binding capacity using ferrous ammonium sulphate.