CD40L activation of human RPE cells
Reviewed by Graham Wallace

Age-related macular degeneration (AMD) is the leading cause of reduced visual acuity in the elderly worldwide. The risk factors involved in AMD include smoking and diet, while genetics have been shown to have a significant role. Recently a link between inflammation and the pathogenesis of AMD has been reported. Activation of the complement system, associated with polymorphisms in the modulating complement factor H gene and antibody deposition, macrophage infiltration of the retina and oxidative injury have all been implicated in AMD. CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions, and its receptor, CD40, have been shown to promote inflammation in many ocular conditions such as diabetic retinopathy. CD40L has further been shown to promote choroidal neovascularisation via macrophage infiltration and release of pro-angiogenic factors. The inflammasome is a protein complex activated by foreign or endogenous danger signals, which leads to maturation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. In this study human retinal pigment epithelial stimulated via CD40L showed activation of components of the inflammasome and IL-1β and IL-18 secretion. IL-1β acting in a paracrine manner induced RPE cells to secrete MCP-1 a chemoattractant for macrophages. These findings that signalling through CD40L can contribute to the low level inflammation characteristic of AMD, and ageing in general. The data further suggest novel targets for treating AMD as such drugs are already being trialled in other diseases.

Distinct CD40L receptors mediate inflammasome activation and secretion of IL-1β and MCP-1 in cultured human retinal pigment epithelial cells.
Bian ZM, Field MG, Elner SG, et al.
EXPERIMENTAL EYE RESEARCH
2018;170:29-39.