Toll-Like Receptors 2 and 4 Polymorphisms in Age-Related Macular Degeneration

Güven, Mehmet; Batar, Bahadır; Mutlu, Tuba; Bostancı, Merve; Mete, Meltem; Aras, Cengiz; Ünal, Mustafa

doi:10.3109/02713683.2015.1067326

Cited by 15 publications

(13 citation statements)

References 34 publications

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“…Consequently, these groups were independently analyzed. Association between TLR4 rs4986791 polymorphism and risk of AMD In total, ve studies, 4,15,16,18,19 including 1714 AMD patients and 1074 controls were focused to assess the impacts of TLR4 rs4986791 polymorphism and AMD susceptibility. The analysis of allelic and genotypic models showed no evidence of an association between this polymorphism and AMD.…”

Section: Resultsmentioning

confidence: 99%

Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis

Roshanipour

Shahriyari

Laleh

et al. 2021

Ophthalmic Genetics

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Section: Resultsmentioning

confidence: 99%

Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis

Roshanipour

Shahriyari

Laleh

et al. 2021

Ophthalmic Genetics

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“…AMD is a multiple factor disease, which is characterized by the development of drusen in Bruch's membrane, the degeneration of RPE and neovascularization. [17,21] Accumulating evidence demonstrates that inflammation seems to play a key role in the development of AMD. [22–24] TLRs play principal roles in immune defense.…”

Section: Discussionmentioning

confidence: 99%

“…[26] TLR4 gene polymorphisms have been reported to be related to ocular diseases, such as AMD. [17,27,28]…”

Section: Discussionmentioning

confidence: 99%

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Associations of TLR4 gene polymorphisms with the risk of age-related macular degeneration in a Chinese Han population

Xiong²

2019

Medicine

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The study was designed to reveal the relationship of toll-like receptor 4 ( TLR4, rs1927914 and rs1927907) polymorphisms with risk of age-related macular degeneration (AMD), as well as the adjustment of this association by some environmental and lifestyle factors in Chinese Han population. TLR4 polymorphisms were genotyped by polymerase chain reaction-restricted fragment length polymorphisms and direct sequencing method in 138 AMD patients and 146 healthy controls. Genotype distribution in the control group was checked with Hardy–Weinberg equilibrium. Association of TLR4 polymorphisms and AMD risk was evaluated by χ 2 test and adjusted by age and sex, smoking and drinking. Odds ratio (OR) with 95% confidence interval (95% CI) was used to represent the association strength. Logistic regressive analysis was used to calculate the adjusted OR values. CC genotype of rs1927914 had significantly lower frequency in AMD patients ( P = .010), indicated a negative association with AMD risk (crude: OR = 0.358, 95% CI = 0.162–0.791; adjusted: OR = 0.355, 95% CI = 0.160–0.789). C allele of rs1927914 might decrease the susceptibility of AMD (crude: OR = 0.698, 95% CI = 0.497–0.982; adjusted: OR = 0.698, 95% CI = 0.495–0.984). No significant association has been discovered between TLR4 rs1927907 polymorphism and AMD susceptibility. Strong linkage disequilibrium existed between rs1927914 and rs1927907 polymorphisms. C-C haplotype was negatively associated with AMD risk (OR = 0.242, 95% CI = 0.121–0.485; OR = 0.242, 95% CI = 0.120–0.488). CC genotype and C allele of rs1927914 were significantly associated with the decreased AMD susceptibility.

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“…Certain polymorphisms of TLR3 are considered to be associated with AMD, though these findings are under debate and may depend on ethnicity [14][15][16]. Furthermore, an association was shown between polymorphisms in TLR2 and 4 and AMD development [17,18]. TLR3 activation may exert toxic effects on RPE cells and increase their VEGF secretion [12,19].…”

Section: Introductionmentioning

confidence: 99%

Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro

Terheyden

Roider

Klettner

2020

Graefes Arch Clin Exp Ophthalmol

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Purpose Systemic inflammation may be of importance in the development of AMD. RPE cells can recognize danger signals with toll-like receptors (TLR) and may react in a pro-inflammatory manner. In this study, we evaluated the basal and apical secretions of TNFα, IL-6, and IL-1β in primary RPE cells and RPE/choroid explant cells under basolateral stimulation of TLR2, 3, and 4; the effects on barrier function; and their influence on neuronal cell viability. Methods RPE/choroid tissue explants were prepared from porcine eyes and cultivated in modified Ussing chambers; primary porcine RPE cells on transwell plates. Cells were basally stimulated with agonists Pam2CSK4 (Pam; TLR2), polyinosinic/polycytidylic acid (Poly I:C; TLR3), and lipopolysaccharide (LPS; TLR4) for 24 h. Supernatants were evaluated with ELISA for cytokines TNFα, IL-6, and IL-1β. Apical supernatants were applied to SHSY-5Y cells, and cell viability was evaluated in MTT assay. Barrier function was tested by measuring transepithelial electrical resistance (TER) and occludin immunostaining. Results None of the tested TLR agonists was toxic on RPE cells after 24 h of exposure. Unstimulated RPE cells secreted hardly any cytokines. Pam induced IL-6, IL-1ß, and TNFα on the basal and apical sides at all concentrations tested. Poly I:C induced IL-6 and TNFα primarily at the basal side at lower but on both sides at higher concentrations. LPS induced IL-6, IL-1ß, and TNFα apically and basally at all concentrations tested. In the RPE/choroid, a strong difference between apical and basal secretions could be found. IL-6 was constitutively secreted basally, but not apically, but was induced by all agonists on both sides. IL-1ß and TNFα alpha were strongly induced on the basal side by all agonists. TER was reduced by all agonists, with Pam and LPS being effective in all concentrations tested. Occludin expression was unaltered, but the distribution was influenced by the agonists, with a less distinct localization at the cell borders after treatment. None of the agonists or supernatants of treated RPE and RPE/choroid organ cultures exerted any effect on viability of SHSY-5Y cells. Conclusions Danger signals activating TLRs can induce polarized cytokine expression and contribute to the loss of barrier function in the RPE.

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Toll-Like Receptors 2 and 4 Polymorphisms in Age-Related Macular Degeneration

Abstract: Our results suggest that TLR2 polymorphism may contribute to the pathogenesis of AMD.

Cited by 15 publications

References 34 publications

Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis

Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis

Associations of TLR4 gene polymorphisms with the risk of age-related macular degeneration in a Chinese Han population

Basolateral activation with TLR agonists induces polarized cytokine release and reduces barrier function in RPE in vitro

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