Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration

Hera, Ruxandra; Kéramidas, Michelle; Péoc’h, Michel; Mouillon, M.; Romanet, Jean-Paul; Feige, Jean‐Jacques

doi:10.1016/j.ajo.2004.11.064

Cited by 77 publications

(51 citation statements)

References 24 publications

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“…31 Angiopoietin 2 also is expressed in surgically excised CNV membranes from neovascular AMD patients. 31,32 Therefore, the Ang2 protein could have a role in the pathogenesis of nAMD and PCV. Recently, in a whole exome sequencing study, by using a genebased mutational load analysis, we and coworkers found that ANGPT2 was nominally associated with AMD (P ¼ 9.85 3 10 À3 ) in the East Asian populations.…”

Section: Discussionmentioning

confidence: 99%

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Brelén

Tsujikawa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Ma L, Brelen ME, Tsujikawa M, et al. Identification of ANGPT2 as a new gene for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in the Chinese and Japanese populations. Invest Ophthalmol Vis Sci. 2017;58:107658: -108358: . DOI:10.1167 PURPOSE. We determine the angiopoietin 2 (ANGPT2) gene as a new susceptibility gene for neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS.A total of 34 haplotype-tagging single-nucleotide polymorphisms (SNPs) were first genotyped in an exploratory Hong Kong Chinese cohort. Suggestive SNPs were replicated in a Shantou Chinese cohort and an Osaka Japanese cohort, with a total of 2343 subjects. The SNP rs800292 in the complement factor H (CFH) gene was genotyped in all the subjects. Genetic association and gene-gene interaction were analyzed.RESULTS. In the Hong Kong cohort, four SNPs in ANGPT2 (rs13255574, rs4455855, rs13269021, and rs11775442) were nominally associated with nAMD and PCV. The four ANGPT2 SNPs showed the same trends of association in the Shantou and Osaka cohorts. Combining the data from the 3 study cohorts revealed that SNPs rs4455855 and rs13269021 achieved study-wise significance (P < 0.0016), conferring an approximately 1.3-fold of increased risk for nAMD and PCV. Interaction analysis revealed the CFH SNP rs800292 has a highly significant interaction with the ANGPT2 SNP rs13269021 in nAMD and PCV in the combined analysis. Subsequent stratification analysis confirmed the interaction.CONCLUSIONS. This study reveals ANGPT2 as a new susceptibility gene for nAMD and PCV, and it may affect disease susceptibility in association with CFH. Thus, this report provides new insights into the genetic architecture of nAMD and PCV.Keywords: ANGPT2, gene association, age-related macular degeneration, polypoidal choroidal vasculopathy, gene-gene interaction A ge-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in the elderly, especially in developed countries. Neovascular AMD (nAMD), a major form of advanced AMD characterized by choroidal neovascularization (CNV), accounts for the majority of severe visual loss in AMD patients. Polypoidal choroidal vasculopathy (PCV) is a macular disease characterized by polyp-like lesions in the choroidal vessels, which are best seen in indocyanine green angiography (ICGA).1 Polypoidal choroidal vasculopathy and nAMD have similarities in clinical manifestations. For example, they can cause submacular hemorrhage, exudation, and scarring, leading to central vision loss. Interestingly, CNV and PCV can present concurrently in approximately 3.23% of patients, 2 suggesting that they may have a shared mechanism. However, while the prevalence of nAMD (approximately 0.46%) is similar between Caucasian and Asian populations, 3 the prevalence of PCV is approximately 3-fold higher in Asians than in Caucasians, 4 suggesting an ethnic background is related to the occurrence of PCV. Moreover, nAMD and PCV respond differentl...

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Section: Discussionmentioning

confidence: 99%

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Brelén

Tsujikawa

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…It is assumed that an altered retina-choriocapillaris barrier leads through a sequence of interrelated events to CNV and ultimately to retinal damage [Zarbin, 2004]. One of these events is the hypoxic condition and thus a lowering of extracellular pH [Goerges and Nugent, 2004] that develops as a consequence of an imbalance between demand and supply of nutrients and oxygen and stimulates the production of neovascularization-inducing VEGF [Pe'er et al, 1995;Mousa et al, 1999;He et al, 2003;Pugh and Ratcliffe, 2003;Hera et al, 2005]. The newly formed vessels that develop under the influence of VEGF are known to be leaky or very leaky (up to hemorrhage) [Campochiaro, 2004;Carmeliet, 2005;Weis and Cheresh, 2005].…”

Section: Relationship Between Ribbons Lsc-like Aggregates and Cnvmentioning

confidence: 99%

New Components of ‘Basal Laminar Deposits’ in Age-Related Macular Degeneration

Reale

Groos

Eckardt

et al. 2008

Cells Tissues Organs

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Two new components of basal laminar deposit (BlamD) occurring in samples of submacular neovascular membranes surgically removed from patients with a wet (exudative) form of age-related macular degeneration are described. They are: (1) minute ribbon-like structures which occur singly and/or in a bunch and extend from the inner surface of the BlamD layer into the extracellular matrix (ECM) beneath the retinal pigment epithelium (RPE). The ribbons are composed of polarized molecules, aggregating in parallel, aligned transversally in register, morphologically similar to isolated collagen molecules of the short-chain type. Deeper in the BlamD but always close to its inner surface, aspects suggesting a transition between ribbons and (2) long-spacing collagen (LSC)-like aggregates characterized by periods bordered by a single dense band were observed. This band could arise from the globular domains of the polarized monomers, which assemble in parallel and display all their terminal extensions at the same end of each period resulting in the single dense band. The presence of ribbons and of LSC-like aggregates in the BlamD layer and the concomitant choroidal neovascularization (CNV) suggest that the events might be correlated. The newly formed vessels crossing Bruch’s membrane and invading the BlamD layer could induce physicochemical changes in the ECM of the RPE, providing the required environmental conditions for the polymerization of collagen molecules into aggregates with the LSC-like pattern. With the deposition of new components, the thickness of BlamD increases and further impairs the supply of nutrients and oxygen, thus sustaining CNV.

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“…No effective treatment or cure is currently available to treat the majority of AMD patients. Increased levels of vascular endothelial growth factor (VEGF) are detected in AMD patients, which can promote the exacerbation of choroidal neovascularization [129]. In fact, in spite of the use of anti-VEGF therapy there is a persistent activity of neovascular lesions [130].…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

Contribution of microglia‐mediated neuroinflammation to retinal degenerative diseases

Boia

Madeira

Aires

et al. 2017

Acta Ophthalmologica

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Retinal degenerative diseases are major causes of vision loss and blindness worldwide and are characterized by chronic and progressive neuronal loss. One common feature of retinal degenerative diseases and brain neurodegenerative diseases is chronic neuroinflammation. There is growing evidence that retinal microglia, as in the brain, become activated in the course of retinal degenerative diseases, having a pivotal role in the initiation and propagation of the neurodegenerative process. A better understanding of the events elicited and mediated by retinal microglia will contribute to the clarification of disease etiology and might open new avenues for potential therapeutic interventions. This review aims at giving an overview of the roles of microgliamediated neuroinflammation in major retinal degenerative diseases like glaucoma, age-related macular degeneration, and diabetic retinopathy.

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Expression of VEGF and angiopoietins in subfoveal membranes from patients with age-related macular degeneration

Cited by 77 publications

References 24 publications

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

Identification of ANGPT2 as a New Gene for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy in the Chinese and Japanese Populations

New Components of ‘Basal Laminar Deposits’ in Age-Related Macular Degeneration

Contribution of microglia‐mediated neuroinflammation to retinal degenerative diseases

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