Toll-Like Receptor Signalling Pathways and the Pathogenesis of Retinal Diseases

Abstract

There is growing evidence that the pathogenesis of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) have a significant chronic inflammatory component. A vital part of the inflammatory cascade is through the activation of pattern recognition receptors (PRR) such as toll-like receptors (TLR). Here, we reviewed the past and current literature to ascertain the cumulative knowledge regarding the effect of TLRs on the development and progression of retinal diseases. There is burgeoning research demonstrating the relationship between TLRs and risk of developing retinal diseases, utilising a range of relevant disease models and a few large clinical investigations. The literature confirms that TLRs are involved in the development and progression of retinal diseases such as DR, AMD, and ischaemic retinopathy. Genetic polymorphisms in TLRs appear to contribute to the risk of developing AMD and DR. However, there are some inconsistencies in the published reports which require further elucidation. The evidence regarding TLR associations in retinal dystrophies including retinitis pigmentosa is limited. Based on the current evidence relating to the role of TLRs, combining anti-VEGF therapies with TLR inhibition may provide a longer-lasting treatment in some retinal vascular diseases.

Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?

“…DAMPs binding to TLR4 activate two distinct downstream signaling pathways that are dependent on MyD88 and TRIF proteins. Both of these molecules have similar effects on angiogenesis and inflammation by activating the NF-κB and MAPK signaling pathways [152][153][154]. The MyD88-dependent signaling pathway leads to the formation of the myddosome complex, which consists of MyD88, IRAK1, and IRAK4 proteins.…”

“…The final consequence of this action is the activation of NF-κB related genes [152]. Recent studies demonstrated that TLR4 signaling pathway generally plays a role in four axes: photo-oxidative stress, cell viability, choroidal neovascularization, and inflammatory pathways [154,[157][158][159]. Moreover, genetic variants associated with TLR4 that affect AMD have been identified [160][161][162].…”

Assessment of Serum Vitamin D Status and Its Associated Health Problem Among Children With Protein Energy Malnutrition: A Cross-Sectional Research Study in Central Rural India

“…The severity and clinical signs of PEM indicate food deficits in marasmus and kwashiorkor. When an individual's susceptibility to infectious diseases increases, which would not typically be fatal, protein-energy deficiency can become a life-threatening condition [5,6].…”

Scarlet Fever – a Diagnostic Challenge for Physicians: a Case Report of Scarlet Fever, Hepatitis, and Sepsis in a 15 –year and 6 month– old Female Adolescent with Severe Acute Malnutrition

“…12 Children with malnutrition are at significantly higher risk of more severe disease and suffer significantly more acute and long-term morbidity and mortality when infected, including scarlet fever. 13 This report is to highlight the importance of early diagnosis and prompt treatment of scarlet fever in a malnourished child to prevent either risk of complications or the spreading of the disease among other children.…”