New findings on pathogenetic mechanisms in the development of age-related macular degeneration

Фурсова, А. Ж.; Derbeneva, A S; Vasilyeva, M A; Nikulich, I F; Tarasov, M S; Gamza, Yu.A.; Chubar, N.V.; Gusarevich, O.G.; Dmitrieva, E.I.; Kozhevnikova, Oyuna S.; Kolosova, N. G.; Elizarova, A.A.

doi:10.17116/oftalma2022138021120

Cited by 7 publications

(3 citation statements)

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“…Due to population ageing, a number of AMD patients is expected to increase by a third in the coming decades [2]. AMD is a progressive disease affecting the macular area due to developing pathological processes in the retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaries [3]. Because of the significant multifactorial nature and complexity of the disease, the exact mechanism of AMD pathogenesis remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration

Kozhevnikova,

Fursova,

Derbeneva

et al. 2023

Biomedicines

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Background: Age-related macular degeneration (AMD) is the leading cause of late-onset blindness in elderly. The occurrence and development of AMD is a multifactorial complex process where autophagy plays an important role. The first-line drugs for neovascular AMD (nAMD) are inhibitors of VEGF, with up to 30% of patients having an incomplete response to treatment. Genetic factors may influence the response to anti-VEGF therapy and explain treatment outcome variability. We aimed to estimate the role of polymorphic markers of the MTOR (rs1064261, rs1057079, rs11121704, rs2295080), SQSTM1 (rs10277), ULK1 (rs11246867, rs3088051), MAP1LC3A (rs73105013) and ATG5 (rs573775) genes in the development of nAMD and the efficacy of anti-VEGF therapy response. Methods: Genotyping by allele-specific PCR was performed in 317 controls and 315 nAMD patients in the Russian population. Of them, 196 treatment-naive nAMD patients underwent three monthly intravitreal injections (IVIs) of aflibercept. Genotypic frequencies were compared with OCT markers of therapy effectiveness and best-corrected visual acuity (BCVA) measures. The main outcomes were the BCVA gain and decrease in central retinal thickness (CRT). Results: MTOR-rs1057079-C, MTOR-rs11121704-C and MTOR-rs2295080-G alleles were associated with an increased risk of nAMD. The BCVA was increased in 117 (59.7%) patients by 10 [5–20] letters, did not changed in 59 (30.1%), and was decreased in 20 (10.2%) patients. ULK1-rs3088051 was associated with BCVA change. Among patients with the TT and CT genotypes for ULK1-rs3088051, an improvement in visual acuity was noted in 67.6% and 53.8% of cases, while in patients with the CC genotype, an increase in BCVA was recorded in 37.5% of cases (p = 0.01). The decrease in CRT was associated with SQSTM1-rs10277 (p = 0.001): it was significantly higher in TT (93 [58–122] mkm) and CT (66 [30–105] mkm) carriers compared to the CC genotype (47 [24–68] mkm). Other SNPs did not show significant associations with the outcome of anti-VEGF treatment. Conclusions: MTOR gene polymorphisms are moderately associated with the risk of nAMD. SQSTM1-rs10277 and ULK1-rs3088051 may influence short-term response to intravitreal anti-VEGF treatment. The results suggest that autophagy could be a target for future drugs to overcome resistance to anti-VEGF therapy.

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Section: Introductionmentioning

confidence: 99%

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration

Kozhevnikova,

Fursova,

Derbeneva

et al. 2023

Biomedicines

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“…Age-related macular degeneration (AMD) is a refractory fundus disease threatening the vision of the global aging population. Neovascular AMD (nAMD) involves new vessels growing into the retinal neurepithelium layer from the choroid capillary through Bruch's membrane/ retinal pigment epithelium [1,2]. nAMD usually rapidly progresses, leading to distortion and disorder of shape, resulting in more cases of legal blindness.…”

Section: Introductionmentioning

confidence: 99%

Determination of Vascular Endothelial Growth Factor-B Concentrations in Aqueous Humor and Plasma of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy Patients Before and After Anti-VEGF Therapy

et al. 2022

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“…Due to the aging of the global population predicted in the coming decades, the number of patients with AMD is expected to increase significantly [2]. AMD is a disease with a complex nature, the development of which is controlled by many interacting genetic and environmental factors that determine the form, rate of disease progression, and response to therapy [3]. The pathogenesis of AMD is based on a decrease in metabolic and regenerative processes characteristic of aging, a violation of the microcirculation and structural organization of the retina, the prerequisites and mechanisms for the transition of which into a pathological process remain unclear [4].…”

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Advanced Research in Age-Related Macular Degeneration: Special Issue

Kozhevnikova

2024

Biomedicines

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New findings on pathogenetic mechanisms in the development of age-related macular degeneration

Cited by 7 publications

References 51 publications

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration

Pharmacogenetic Association between Allelic Variants of the Autophagy-Related Genes and Anti-Vascular Endothelial Growth Factor Treatment Response in Neovascular Age-Related Macular Degeneration

Determination of Vascular Endothelial Growth Factor-B Concentrations in Aqueous Humor and Plasma of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy Patients Before and After Anti-VEGF Therapy

Advanced Research in Age-Related Macular Degeneration: Special Issue

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