Progression From No AMD to Intermediate AMD as Influenced by Antioxidant Treatment and Genetic Risk

2017 ◽  
Vol 1 (1) ◽  
pp. 45-51
Author(s):  
Carl C. Awh ◽  
Brent Zanke ◽  
Rafal Kustra
Keyword(s):  
Genetic Risk ◽  
Factor H ◽  
Complement Factor ◽  
Antioxidant Treatment ◽  
Risk Alleles ◽  
High Genetic Risk ◽  
Age Related ◽  
Allele Dosage ◽  
Risk Of Progression ◽  
The Impact

Purpose: To investigate the impact of antioxidant treatment and genetic risk on the development of intermediate age-related macular degeneration (AMD) in patients without baseline AMD, using data from the Age-Related Eye Disease Study (AREDS) Cataract Trial. Methods: Genetic risk and antioxidant treatment were analyzed as independent and interacting risk factors for the development of intermediate AMD in 554 AREDS individuals for whom genotyping was available. Genetic risk was determined using an allele dosage model based on the total number of complement factor H and age-related maculopathy sensitivity 2 risk alleles. Results: Overall, 14% of patients developed intermediate AMD over approximately 8 years. The risk of developing intermediate AMD varied from 6.5% for patients with 0 risk alleles to 39% for those with 3 or 4 risk alleles ( P < .0001). Antioxidants had no impact on the development of intermediate AMD overall. However, antioxidant treatment had a significant impact on progression to intermediate AMD for patients with low or high genetic risk. Patients with 0 or 1 risk alleles had increased risk of progression to intermediate AMD (hazard ratio [HR] = 2.31, P = .017) if treated with antioxidants compared to placebo. Patients with 3 or 4 risk alleles had decreased risk of progression to intermediate AMD (HR = 0.27, P = .0008) if treated with antioxidants compared to placebo. Conclusion: On average, antioxidant treatment has no impact on the development of intermediate AMD in patients without AMD. However, antioxidant treatment may increase the risk of developing intermediate AMD in patients with low genetic risk and may reduce the risk of developing intermediate AMD in patients with high genetic risk. Since patients with high genetic risk have the greatest risk of progressing from intermediate to advanced AMD, genotype-directed antioxidant treatment of patients without AMD may ultimately lead to fewer cases of advanced AMD.

Benefits, Potential Harms, and Optimal Use of Nutritional Supplementation for Preventing Progression of Age-Related Macular Degeneration

2016 ◽  
Vol 51 (3) ◽  
pp. 264-270 ◽  
Author(s):  
Carlos H. Rojas-Fernandez ◽  
Kevin Tyber
Keyword(s):  
Genetic Testing ◽  
Macular Degeneration ◽  
Therapeutic Use ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Supplement Use ◽  
Risk Alleles ◽  
Mesh Terms ◽  
Age Related

Objective: To briefly review age-related macular degeneration (AMD), the main findings from the Age Related Eye Disease Study (AREDS) report number 8 on the use of nutritional supplements for AMD, and to focus on data suggesting that supplement use should be guided using genetic testing of AMD risk genes. Data Sources: A literature search (January 2001 through October 26, 2016) was conducted using MEDLINE and the following MeSH terms: Antioxidants/therapeutic use, Genotype, Macular Degeneration/drug therapy, Macular degeneration/genetics, Dietary Supplements, Proteins/genetics, and Zinc Compounds/therapeutic use. Bibliographies of publications identified were also reviewed. Study Selection and Data Extraction: English-language studies assessing AREDS supplement response in patients with AMD in relation to complement factor H gene ( CFH) and age-related maculopathy susceptibility 2 gene ( ARMS2) risk alleles were evaluated. Data Synthesis: Three of the 4 studies demonstrated a treatment interaction between ARMS2 and CFH genotypes and a differential response to supplements. The fourth study documented an interaction for the CFH genotype only. Reported response interactions included attenuated response, no response, and good response, whereas a subset showed increased progression of AMD. Conversely, one study reported no interactions between CFH and ARMS2 risk alleles and response to supplements. Conclusions: The weight of the evidence supports using genetic testing to guide selection of ocular vitamin use. This approach will avoid using supplements that could speed the progression of AMD in vulnerable patients, avoid using supplements that will have little to no effect in others, and result in appropriately using supplements in those that are likely to derive meaningful benefits.

Complement factor H R1210C among Japanese patients with age-related macular degeneration

2015 ◽  
Vol 59 (5) ◽  
pp. 273-278 ◽  
Author(s):  
Masahiro Miyake ◽  
Masaaki Saito ◽  
Kenji Yamashiro ◽  
Tetsuju Sekiryu ◽  
Nagahisa Yoshimura
Keyword(s):  
Macular Degeneration ◽  
Japanese Patients ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related

scholarly journals Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 622
Author(s):  
Iswariyaraja Sridevi Gurubaran ◽  
Hanna Heloterä ◽  
Stephen Marry ◽  
Ali Koskela ◽  
Juha M. T. Hyttinen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mouse Model ◽  
Macular Degeneration ◽  
Complement Component ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Related Factor ◽  
Complement Factor ◽  
Age Related ◽  
Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

LOC387715/HTRA1 and Complement Factor H Variants in Patients with Age-Related Macular Degeneration Seen at the Mayo Clinic

2007 ◽  
Vol 28 (4) ◽  
pp. 203-207 ◽  
Author(s):  
Jose S. Pulido ◽  
Lisa M. Peterson ◽  
Lejla Mutapcic ◽  
Sandra Bryant ◽  
W. Edward Highsmith
Keyword(s):  
Macular Degeneration ◽  
Mayo Clinic ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Complement Factor H ◽  
Complement Factor ◽  
Age Related
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