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

Int Ophthalmol. 2023 Dec;43(12):4869-4878. doi: 10.1007/s10792-023-02889-7. Epub 2023 Nov 8.

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.

Keywords: Dry age-related macular degeneration; NLRP12; NLRP3; NOD-like receptors; Pathogenesis.

MeSH terms

  • Aged
  • Geographic Atrophy* / diagnosis
  • Humans
  • Inflammation
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukocytes, Mononuclear
  • Mitochondrial Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Wet Macular Degeneration* / diagnosis
  • Wet Macular Degeneration* / genetics

Substances

  • Mitochondrial Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRX1 protein, human
  • NLRP12 protein, human
  • Intracellular Signaling Peptides and Proteins