Toll-Like Receptors and Age-Related Macular Degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the over 50s worldwide. Activation of the immune system has been implicated in disease progression, but while polymorphisms in genes associated with the immune system have been identified as risk factors for disease, the underlying pathways and mechanisms involved in disease progression remain incompletely characterised. Typically inflammatory responses are mediated by microbial infection; however, in chronic conditions, a form of 'sterile' inflammation exists whereby immune responses occur in areas of the body, in the absence of microbes; 'sterile' inflammation is likely to be central to AMD. In this case the innate immune response is triggered when alarm signals released by stressed cells or damaged tissue are identified by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are a family of membrane-spanning PRRs for which host-derived ligands have been identified; these include heat shock proteins, extracellular matrix breakdown products, mRNA from necrotic cells and modified lipids. Here we review the evidence for TLR involvement in the pathogenesis of AMD.

Ocular surface toll like receptors in ageing

“…Sterile inflammation occurs in response to a growing list of modified host-derived elements ranging from oxidized lipids or lipoproteins to deposits of protein/lipid aggregates or particulate matter [24]. These stimuli trigger activation of PRRs of the innate immune system, such as TLRs [28].…”

Toll-Like Receptors in InflammAging at Ocular Surface.

“…23 These stimuli trigger activation of pattern recognition receptors (PRRs) of the innate immune system. 27 In fact frequently these stimuli are often easily cleared, leading to a self-limiting and controlled homeostatic para-inflammation. But, once such system is dysregulated, the inflammatory response can persist causing over-activation of the immune system and contributing to disease pathogenesis.…”

Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

“…DAMPs and PAMPs released by injured retinal cells are recognized by PRRs such as TLRs. The interaction of DAMPS with TLRs has been highly explored in retinal disorders ( Figure 2 ), including endophthalmitis, uveitis, glaucoma, ischemia-reperfusion injury, DR, and AMD [ 4 , 11 , 264 , 265 , 266 , 267 ]. It is interesting to note that TLR2 function in light-induced retinal degeneration showed sex dependency.…”