Pigment Epithelium-Derived Factor Gene Met72Thr Polymorphism Is Associated With Increased Risk of Wet Age-related Macular Degeneration

2008 ◽  
Vol 145 (4) ◽  
pp. 716-721.e2 ◽  
Author(s):  
Jane-Ming Lin ◽  
Lei Wan ◽  
Yi-Yu Tsai ◽  
Hui-Ju Lin ◽  
Yushin Tsai ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Factor Gene ◽  
Pigment Epithelium Derived Factor ◽  
Age Related ◽  
Increased Risk

Met72Thr polymorphism of pigment epithelium-derived factor gene and susceptibility to age-related macular degeneration

2005 ◽  
Vol 64 (6) ◽  
pp. 1202-1204 ◽  
Author(s):  
S. Yamagishi ◽  
K. Nakamura ◽  
H. Inoue ◽  
M. Takeuchi
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Age Related Macular Degeneration ◽  
Factor Gene ◽  
Pigment Epithelium Derived Factor ◽  
Age Related

scholarly journals Calcified nodules in retinal drusen are associated with disease progression in age-related macular degeneration

2018 ◽  
Vol 10 (466) ◽  
pp. eaat4544 ◽  
Author(s):  
Anna C. S. Tan ◽  
Matthew G. Pilgrim ◽  
Sarah Fearn ◽  
Sergio Bertazzo ◽  
Elena Tsolaki ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Human Eye ◽  
Age Related ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Retinal Drusen ◽  
Independent Cohort

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

scholarly journals Significant Association Between Variant in SGCD and Age-Related Macular Degeneration

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 467 ◽  
Author(s):  
Andric Christopher Perez-Ortiz ◽  
Alexandra Luna-Angulo ◽  
Juan Carlos Zenteno ◽  
Alvaro Rendon ◽  
Liliana Guadalupe Cortes-Ballinas ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Case Control Study ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Case Control ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Increased Risk ◽  
History Of ◽  
Control Study

CFH and HTRA1 genes are traditional markers of increased risk of age-related macular degeneration (AMD) across populations. Recent findings suggest that additional genes—for instance, in the dystrophin-associated protein complex—might be promising markers for AMD. Here, we performed a case-control study to assess the effect of SGCD single nucleotide polymorphisms (SNPs), a member of this protein family, on AMD diagnosis and phenotype. We performed a case-control study of an under-studied population from Hispanics in Mexico City, with 134 cases with 134 unpaired controls. Cases were 60 years or older (Clinical Age-Related Maculopathy Staging (CARMS) grade 4–5, as assessed by experienced ophthalmologists following the American Association of Ophthalmology (AAO) guidelines), without other retinal disease or history of vitreous-retinal surgery. Controls were outpatients aged 60 years or older, with no drusen or retinal pigment epithelium (RPE) changes on a fundus exam and a negative family history of AMD. We examined SNPs in the SGCD gene (rs931798, rs140617, rs140616, and rs970476) by sequencing and real-time PCR. Genotyping quality checks and univariate analyses were performed with PLINK v1.90b3.42. Furthermore, logistic regression models were done in SAS v.9.4 and haplotype configurations in R v.3.3.1. After adjusting for clinical covariates, the G/A genotype of the SGCD gene (rs931798) significantly increases the odds of being diagnosed with AMD in 81% of cases (1.81; 95% CI 1.06–3.14; p = 0.031), especially the geographic atrophy phenotype (1.82; 95% CI 1.03–3.21; p = 0.038) compared to the G/G homozygous genotype. Moreover, the GATT haplotype in this gene (rs931798, rs140617, rs140616, and rs970476) is associated with lower odds of AMD (adjusted odds ratio (OR) 0.13; 95% CI 0.02–0.91; p = 0.041). SGCD is a promising gene for AMD research. Further corroboration in other populations is warranted, especially among other Hispanic ethnicities.

Adenoviral Vector-Delivered Pigment Epithelium-Derived Factor for Neovascular Age-Related Macular Degeneration: Results of a Phase I Clinical Trial

2006 ◽  
Vol 0 (0) ◽  
pp. 060123080936011
Author(s):  
Peter A. Campochiaro ◽  
Quan Dong Nguyen ◽  
Syed Mahmood Shah ◽  
Michael L. Klein ◽  
Eric Holz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Macular Degeneration ◽  
Adenoviral Vector ◽  
Pigment Epithelium ◽  
Phase I Clinical Trial ◽  
Age Related Macular Degeneration ◽  
Pigment Epithelium Derived Factor ◽  
Age Related

Adenoviral Vector-Delivered Pigment Epithelium-Derived Factor for Neovascular Age-Related Macular Degeneration: Results of a Phase I Clinical Trial

2006 ◽  
Vol 17 (2) ◽  
pp. 167-176 ◽  
Author(s):  
Peter A. Campochiaro ◽  
Quan Dong Nguyen ◽  
Syed Mahmood Shah ◽  
Michael L. Klein ◽  
Eric Holz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Macular Degeneration ◽  
Adenoviral Vector ◽  
Pigment Epithelium ◽  
Phase I Clinical Trial ◽  
Age Related Macular Degeneration ◽  
Pigment Epithelium Derived Factor ◽  
Age Related

scholarly journals Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Age Related Macular Degeneration, Role in Pathophysiology, and Possible New Therapeutic Strategies

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1170
Author(s):  
Valentina Bilbao-Malavé ◽  
Jorge González-Zamora ◽  
Miriam de la Puente ◽  
Sergio Recalde ◽  
Patricia Fernandez-Robredo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Increased Risk

Age related macular degeneration (AMD) is the main cause of legal blindness in developed countries. It is a multifactorial disease in which a combination of genetic and environmental factors contributes to increased risk of developing this vision-incapacitating condition. Oxidative stress plays a central role in the pathophysiology of AMD and recent publications have highlighted the importance of mitochondrial dysfunction and endoplasmic reticulum stress in this disease. Although treatment with vascular endothelium growth factor inhibitors have decreased the risk of blindness in patients with the exudative form of AMD, the search for new therapeutic options continues to prevent the loss of photoreceptors and retinal pigment epithelium cells, characteristic of late stage AMD. In this review, we explain how mitochondrial dysfunction and endoplasmic reticulum stress participate in AMD pathogenesis. We also discuss a role of several antioxidants (bile acids, resveratrol, melatonin, humanin, and coenzyme Q10) in amelioration of AMD pathology.

scholarly journals Chromosome 10q26–driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium

2021 ◽  
Vol 118 (30) ◽  
pp. e2103617118
Author(s):  
Brandi L. Williams ◽  
Nathan A. Seager ◽  
Jamie D. Gardiner ◽  
Chris M. Pappas ◽  
Monica C. Cronin ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Association Studies ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Genome Wide Association Studies ◽  
Protective Function ◽  
Age Related ◽  
Increased Risk

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151–171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389–407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227–3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE–Bruch’s membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE–BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD.

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