PAF‐induced inflammatory and immuno‐allergic ophthalmic diseases and their mitigation with PAF receptor antagonists: Cell and nuclear effects

Abstract

Ocular allergies are becoming more prevalent as more airborne pollutants, irritants and microbes pervade our environment. Inflammatory and allergic mediators released by dendritic and mast cells within the conjunctiva cause allergic conjunctivitis (AC), a prevalent ocular surface disorder that affects >40% of the world's human population on a seasonal or perennial basis. Even though histamine is a major culprit, platelet‐activating factor (PAF) also contributes to AC, acting either directly or synergistically with histamine and other mediators. PAF receptor‐meditated inflammatory reactions, via cell‐membrane‐bound and nuclear‐membrane‐bound and nuclear PAF receptors, are also implicated in the etiology of other eye diseases such as uveitis, diabetic retinopathy, corneal and choroidal neovascularization, and age‐related macular degeneration which cause serious visual impairment and can lead to blindness. This review highlights the various deleterious elements implicated in the pathological aspects of ocular allergic reactions and inflammation and provides concepts and treatment options to mitigate these eye disorders with a special focus on PAF and PAF receptor antagonists.

Platelet Activating Factor (PAF): A Mediator of Inflammation

“…PAF and PAF‐R are widely distributed in the structures of the eye, and PAF has been detected in the tear film. PAF has been implicated in the pathogenesis of multiple ocular disorders including allergic conjunctivitis, macular degeneration, ocular pain, uveitis, and diabetic complications of retinopathy and neovascularization 93 …”

“…PAF has been implicated in the pathogenesis of multiple ocular disorders including allergic conjunctivitis, macular degeneration, ocular pain, uveitis, and diabetic complications of retinopathy and neovascularization. 93…”

Platelet‐activating factor as an endogenous cofactor of food anaphylaxis

“…PAF is implicated in physiological processes (apoptosis, wound healing, reproduction, neovascularization, physiological inflammation) and multitude of pathological processes such as cancers, cardiovascular diseases, renal diseases, cerebrovascular and central nervous system disorders, infections, inflammation in sepsis, acute pancreatitis, ocular diseases, asthma, and allergies. [37][38][39][40][41][42] A recent research has investigated the role of PAF in COVID-19 pathogenesis. Interestingly, the coronavirus spike protein modulates the PAF production.…”

“…It has been established that this factor can modulate the production of mediators such as prostaglandins, cytokines, and other inflammatory factors. 48 T A B L E 1 PAF in food anaphylaxis.…”

Platelet activating factor: Have we been missing the forest for the trees?

“…PAF has many potent biological effects, 10,11 including promotion of inflammation 6,11–14 . PAF induces IL‐6 production 15–17 and then IL‐6 stimulates production of PAF 18,19 .…”