New approaches and potential treatments for dry age-related macular degeneration

Damico, Francisco Max; Gasparin, Fabio; Scolari, Mariana Ramos; Pedral, Lycia Sampaio; Takahashi, Beatriz Sayuri

doi:10.1590/s0004-27492012000100016

Cited by 42 publications

(37 citation statements)

References 43 publications

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“…6 Although a number of agents are available to treat exudative ('wet') AMD, prevention of the disease continues to be more challenging. 8,9 The pathogenesis of AMD remains indeterminate and is likely to be multifactorial. 10 The disease is related to well-known risk factors, such as cigarette smoking, elevated serum cholesterol levels, and hypertension, that are shared with atherosclerosis and consequently with increased risk of cardiovascular disease (CVD).…”

Section: Introductionmentioning

confidence: 99%

Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005–2008

Barbosa

Mendes

Cíntron-Colon

et al. 2014

Eye

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Purpose To determine the association of hydroxymethylglutarylcoenzyme A (HMG Co-A) reductase inhibitor (statin) use with the prevalence of age-related macular degeneration (AMD). Methods This cross-sectional study included 5604 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008, Z40 years of age, who were ascertained with regard to the diagnosis of AMD, the use of statins, and comorbidities and health-related behaviors such as smoking. Results The mean age of participants denying or confirming a history of AMD was 68 (SEM 0.90) and 55 (SEM 0.36) years, respectively. Individuals 68 years of age or older who were classified as long-term users of statins had statistically significant less self-reported AMD (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.49-0.84; P ¼ 0.002), after adjusting for potential confounding variables. No significant association was found between the prevalence of AMD and statin consumption among subjects between 40 and 67 years of age (OR 1.61, 95% CI 0.85-3.03; P ¼ 0.137). Conclusions Our results suggest a possible beneficial effect of statin intake for the prevention of AMD in individuals 68 years of age or older.

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Section: Introductionmentioning

confidence: 99%

Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005–2008

Barbosa

Mendes

Cíntron-Colon

et al. 2014

Eye

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“…Approximately 10-18% of individuals between 65 and 75 years old have lost some central vision as a result of AMD (5,12,14). Although neovascular AMD is the most damaging form of the disease, atrophic AMD accounts for approximately 90% of all cases (reviewed in (15)). …”

Section: Introductionmentioning

confidence: 99%

“…Over the last years, a significant amount of research has been focused on the physiopathology of atrophic AMD and new treatment approaches. However, research has been hampered by some issues, such as the multifactorial nature of atrophic AMD, its complex physiopathology, the lack of a suitable animal model, and the lack of in vitro systems for testing new drugs (reviewed in (15)). Currently, the only approved treatment for atrophic AMD is the use of the Age Related Eye Disease Study formulation.…”

Section: Introductionmentioning

confidence: 99%

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Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Swaminathan

Palamoor

et al. 2014

AAPS J

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Abstract. Asialo, tri-antennary oligosaccharide (NA3 glycan) is an endogenous compound, which supports proper folding of outer segment membranes, promotes normal ultrastructure, and maintains protein expression patterns of photoreceptors and Müller cells in the absence of retinal pigment epithelium support. It is a potential new therapeutic for atrophic age-related macular degeneration (AMD) and other retinal degenerative disorders. Herein, we evaluate the safety, in vitro stability, ocular pharmacokinetics and biodistribution of NA3. NA3 was injected into the vitreous of New Zealand white rabbits at two concentrations viz. 1 nM (minimum effective concentration (MEC)) and 100 nM (100XMEC) at three time points. Safety was evaluated using routine clinical and laboratory tests. Ocular pharmacokinetics and biodistribution of [ 3 H]NA3 were estimated using scintillation counting in various parts of the eye, multiple peripheral organs, and plasma. Pharmacokinetic parameters were estimated by non-compartmental modeling. A 2-aminobenzamide labeling and hydrophilic interaction liquid interaction chromatography were used to assess plasma and vitreous stability. NA3 was well tolerated by the eye. The concentration of NA3 in eye tissues was in the order: vitreous>retina>sclera/choroid> aqueous humor>cornea>lens. Area under the curve (0 to infinity) (AUC∞) was the highest in the vitreous thereby providing a positive concentration gradient for NA3 to reach the retina. Half-lives in critical eye tissues ranged between 40 and 60 h. NA3 concentrations were negligible in peripheral organs. Radioactivity from [ 3 H]NA3 was excreted via urine and feces. NA3 was stable at 37°C in vitreous over a minimum of 6 days, while it degraded rapidly in plasma. Collectively, these results document that NA3 shows a good safety profile and favorable ocular pharmacokinetics.

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“…The results of these studies show that oxidative stress is the important factor for ARMD progression. 18 It has been shown that ARMD affects the macula, the posterior aspect of the retina responsible for central visual acuity. 4 The retina is an ideal environment for the generation of ROS for several reasons.…”

mentioning

confidence: 99%

Asymmetric dimethylarginine and homocysteine in exudative age-related macular degeneration

Javadzadeh¹,

Ghorbanihaghjo²,

Mansouri³

et al. 2015

J anal res clin med

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Citation: Javadzadeh A, Ghorbanihaghjo A, Manzouri S, Rashtchizadeh N. Asymmetric dimethylarginine and homocysteine in exudative age-related macular degeneration. J Anal Res Clin Med 2015; 3(4): 236-43. Doi: 10.15171/jarcm.2015.037 Age-related macular degeneration (ARMD) is the leading cause of blindness particularly in elderly people throughout the world. 1 It affects about 25% of people over 65, and the incidence is likely to rise as an outcome of increasing longevity. 2,3 ARMD is not painful, however, it affects the central vision and patients with ARMD may have blurred vision (early ARMD), or even a total loss of central vision (advanced ARMD), and they cannot see things in details. 4 The loss of central vision caused by ARMD can decrease quality of life by severely affecting basic daily tasks such as reading, driving, and facial recognition. In addition, approximately onethird of patients with ARMD suffer from depression. 1 The disease is complex and multifactorial; also several risk factors are associated with its development. Some recognized risk factors are age, white race, heredity, exposure to light, smoking, andThe oxidative stress has been proposed as an important case of exudative agerelated macular degeneration (E-ARMD). The aim of the present study was to investigate homocysteine (Hcy), asymmetric dimethylarginine (ADMA) and oxidized low-density lipoprotein cholesterol (Ox-LDL-C) levels, the factors involved in oxidative stress, in the patients with E-ARMD.In a cross-sectional study, 45 patients with E-ARMD were compared with 45 sex-and age-matched healthy controls. The levels of biochemical factors, Hcy, ADMA, and of Ox-LDL were estimated by standard methods in both study groups.The levels of Hcy (15.4 ± 7.2 vs. 10.7 ± 3.7 μM, P = 0.001), Ox-LDL (52.2 ± 13.8 vs. 37.8 ± 10.8 U/l, P = 0.001), and ADMA (0.84 ± 0.23 vs. 0.71 ± 0.26 μM, P = 0.012) were significantly higher in the patients with E-ARMD than those in the controls. In the patient group, there was a positive and significant correlation between serum Ox-LDL and Hcy concentrations (r = 0.719, P = 0.001), but no correlation was found between serum ADMA and Ox-LDL (r = 0.010, P = 0.900) and also between serum Hcy and ADMA levels (r = -0.070, P = 0.600).The high levels of Hcy as an oxidant agent and ADMA as an endogenous nitric oxide synthase inhibitor can lead to increase Ox-LDL levels, and they may have important roles in oxidative stress, which can be a trigger in E-ARMD.

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New approaches and potential treatments for dry age-related macular degeneration

Cited by 42 publications

References 43 publications

Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005–2008

Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005–2008

Novel Endogenous Glycan Therapy for Retinal Diseases: Safety, In Vitro Stability, Ocular Pharmacokinetic Modeling, and Biodistribution

Asymmetric dimethylarginine and homocysteine in exudative age-related macular degeneration

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