Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty

Int J Mol Sci. 2021 Nov 12;22(22):12268. doi: 10.3390/ijms222212268.

Abstract

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

Keywords: aqueous humor; corneal transplantation; cytokine; glaucoma; intraocular pressure; iris atrophy; penetrating keratoplasty; peripheral anterior synechia.

MeSH terms

  • Animals
  • Aqueous Humor / metabolism*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Eye Diseases / etiology
  • Eye Diseases / metabolism*
  • Eye Diseases / physiopathology
  • Humans
  • Intraocular Pressure / physiology
  • Keratoplasty, Penetrating / adverse effects
  • Keratoplasty, Penetrating / methods*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred DBA
  • Prospective Studies
  • Tomography, Optical Coherence

Substances

  • Cytokines