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Association of NLRPs with pathogenesis of dry age-related macular degeneration

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Abstract

Background

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and Dry AMD is the most common clinical subtype. However, effective measures for the early diagnosis and treatment of dry AMD have not been proposed. In recent years, NOD-like receptors (NLRs) have received attention in the study of AMD as an important class of pattern recognition receptors. We attempted to elucidate the pathogenesis of NLRs in dry AMD from the perspective of chronic inflammation.

Methods

This study involved 13 patients with dry AMD, 10 age- and sex-matched normal population without any history of disease and 8 patients with wet AMD as controls. Using RT-qPCR, the mRNA expression levels of NLRs in peripheral blood peripheral blood mononuclear cells (PBMCs) were compared to analyze the statistical differences in the expression contents among the three populations.

Results

The relative RNA expression of nucleotide-binding oligomerization-like receptor protein 12 (NLRP12) with negative regulation of inflammation was significantly lower in dry AMD patients than in normal people and wet AMD patients. And NLRX1, which also has an anti-inflammatory effect, was lower in dry AMD patients than in wet AMD patients. However, NLRP3 with proinflammatory effect was significantly expressed in wet AMD.

Conclusion

The significant decrease in NLRP12 in dry AMD may become a breakthrough in the study of dry AMD and systemic chronic inflammatory response. However, NLRP3 may have a more important role in wet AMD.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. Yu W, Dong S, Zhao C, Wang H, Dai F, Yang J (2013) Cumulative association between age-related macular degeneration and less studied genetic variants in PLEKHA1/ARMS2/HTRA1: a meta and gene-cluster analysis. Mol Biol Rep 40(10):5551–5561

    Article  CAS  PubMed  Google Scholar 

  2. Yokota K, Miyazaki T, Hemmatazad H, Gay RE, Kolling C, Fearon U et al (2012) The pattern-recognition receptor nucleotide-binding oligomerization domain-cotaining protein 1 promotes production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 64:1329–1337

    Article  CAS  PubMed  Google Scholar 

  3. Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K (2016) Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci 73:1765–1786

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ong BB, Ah-Fat FG (2016) Age-related macular degeneration. Br J Hosp Med ( Lond) 77:C18–C21

    Article  CAS  PubMed  Google Scholar 

  5. Nowak JZ (2006) Age-related macular degeneration(AMD): pathogenesis and therapy. Pharmacol Rep 58:353–363

    CAS  PubMed  Google Scholar 

  6. Johnson LV, Ozaki S, Staples MK Erickson PA, Anderson DH (2000) A potential role for immune complex pathogenesis in drusen formation. Exp Eye Res 70:441–449

  7. Kijlstra A, La Heij E, Hendrikse F (2005) Immunological factors in the pathogenesis and treatment of age-related macular degeneration. Ocul Immunol Inflamm 13:3–11

    Article  CAS  PubMed  Google Scholar 

  8. Kaarniranta K, Salminen A (2009) Age-related macular degeneration: activation of innate immunity system via pattern recognition receptors. J Mol Med 87:117–123

    Article  CAS  PubMed  Google Scholar 

  9. Paul A, Mark E (2014) The immune system and AMD. Curr Ophthalmol Rep 2:14–19

    Article  Google Scholar 

  10. Miller DM, Espinosa-Heidmann DG, Legra J, Dubovy SR, Sũner IJ, Sedmak DD et al (2004) The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am J Ophthalmol 138:323–328

    Article  PubMed  Google Scholar 

  11. Kalayoglu MV, Bula D, Arroyo J, Gragoudas ES, D'Amico D, Miller JW (2005) Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthal 243:1080-1-90

  12. Robman L, Mahdi OS, Wang JJ, Burlutsky G, Mitchell P, Byrne G et al (2007) Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci 48:4007–4011

    Article  PubMed  Google Scholar 

  13. Zhu Y, Qian D, Zhong M, Peng H (2014) Expression and significance of toll-like receptors in peripheral blood mononuclear cells of patients with wet age-related macular degeneration. J Chongqing Med Univ 39:34–38

    CAS  Google Scholar 

  14. Schertzer JD, Tamrakar AK, Magalhaes JG, Pereira S, Bilan PJ, Fullerton MD et al (2011) NOD1 activators link innate immunity to insulin resistance. Diabetes 60:2206–2215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Deng B, Ye Z, Li L, Zhang D, Zhu Y, He Y et al (2016) Higher expression of NOD1 and NOD2 is associated with Vogt-Koyanagi-Harada (VKH) syndrome but not Behcet’s Disease (BD). Curr Mol Med 16:424–435

    Article  CAS  PubMed  Google Scholar 

  16. Hume GE, Fowler EV, Doecke J, Simms LA, Huang N, Palmieri O et al (2008) Novel NOD2 haplotype strengthens the association between TLR4 Asp299gly and Crohn’s disease in an Australian population. Inflamm Bowel Dis 14:585–590

    Article  PubMed  Google Scholar 

  17. Kim YK, Shin JS, Nahm MH (2016) NOD-like receptors in infection, immunity, and diseases. Yonsei Med J 57:5–14

    Article  CAS  PubMed  Google Scholar 

  18. Fekete T, Bencze D, Bíró E, Benkő S, Pázmándi K (2021) Focusing on the cell type specific regulatory actions of NLRX1. Int J Mol Sci 22:1316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goldberg EL, Dixit VD (2015) Drivers of age-related inflammation and strategies for healthspan extension. Immunol Rev 265:63–74

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vandanmagsar B, Youm YH, Ravussin A, Galgani JE, Stadler K, Mynatt RL et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Anand PK, Malireddi RK, Lukens JR, Vogel P, Bertin J, Lamkanfi M (2012) NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488:389–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wei L, Liu B, Tuo J, Shen D, Chen P, Li Z et al (2012) Hypomethylation of the IL17RC promoter associates with age-related macular degeneration. Cell Rep 2:1151–1158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Edwards AO, Ritter R, Abel KJ, Manning A, Panhuysen C (2005) Complement factor H polymorphism and age-related macular degeneration. Science 308:421–424

    Article  CAS  PubMed  Google Scholar 

  24. Hageman GS, Anderson DH, Johnson LV, Hancox LS, Taiber AJ, Hardisty LI et al (2005) A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes population to age-related macular degeneration. Proc Natl Acad 102:7227–7222

    Article  CAS  Google Scholar 

  25. Doyle SL, Campbell M, Ozaki E, Salomon RG, Mori A, Kenna PF et al (2012) NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat Med 18:791–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tarallo V, Hirano Y, Gelfand BD, Dridi S, Kerur N, Kim Y et al (2012) DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 149:847–859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liu B, Wei L, Meyerle C, Tuo J, Sen HN, Li Z et al (2011) Complement component C5a promotes expression of IL- 22 and IL-17 from human T cells and its implication in age- related macular degeneration. J Transl Med 9:1–12

    Article  CAS  PubMed  Google Scholar 

  28. Ardeljan D, Wang Y, Park S Shen D, Chu XK, Yu CR, et al (2014) Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker:implications for age-related macular degeneration. PLoS ONE. 9:e95900

  29. Chen Y, Zhong M, Liang L, Gu F, Peng H (2014) Interleukin-17 induces angiogenesis in human Choroidal endothelial cells in vitro. Investig Ophthalmol Vis Sci 55:6968–6975

    Article  CAS  Google Scholar 

  30. Zhang S, Liu Y, Lu S, Cai X (2015) Genetic variants of interleukin-17A are functionally associated with increased risk of age-related macular degeneration. Inflammation 38:658–663

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the National University Basic funding (Grant No. ZYGX2018J098), the Youth Scientific Research Fund of Sichuan Provincial People's Hospital (Grant No. 2017QN02), and the Scientific Research Project of Sichuan Provincial People's Hospital (Grant No. 2021kflx007), Projects of Sichuan Provincial Science and Technology Department (Grant No. 23ZDYF1942).

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Authors and Affiliations

Authors

Contributions

Conceptualization and methodology were contributed by W.Z. and B.D.; experiment processing was contributed by Y.Z., W.D. and W.Z.; formal analysis, data curation, and statistical analysis were contributed by Y.Z.; writing—original draft preparation, was contributed by Y.Z.; writing—review and editing, was contributed by Y.Z., W.D. and B.D.; supervision and project management were contributed by W.Z. and B.D. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Wanqiu Zhang or Bolin Deng.

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The authors declare that there is no conflict of interest associated with the manuscript.

Ethical approval

This study has been approved by the Ethical Committee of Sichuan Provincial People's Hospital. Samples were collected after people signed informed consent and samples were all collected from Sichuan Provincial People's Hospital.

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Zeng, Y., Dong, W., Zhang, W. et al. Association of NLRPs with pathogenesis of dry age-related macular degeneration. Int Ophthalmol 43, 4869–4878 (2023). https://doi.org/10.1007/s10792-023-02889-7

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  • DOI: https://doi.org/10.1007/s10792-023-02889-7

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