Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders

Abstract

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. Recent evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, high glucose, oxidative stress, ischemia, mechanical trauma, stress, or environmental conditions, in retinal diseases. DAMPs activate the innate immune system, suggesting their role to be protective, but may promote pathological inflammation and angiogenesis in response to the chronic insult or injury. DAMPs are recognized by specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs) and the NOD-like receptor family (NLRs), and purine receptor 7 (P2X7), in systemic diseases. However, studies describing the role of DAMPs in retinal disorders are meager. Here, we extensively reviewed the role of DAMPs in retinal disorders, including endophthalmitis, uveitis, glaucoma, ocular cancer, ischemic retinopathies, diabetic retinopathy, age-related macular degeneration, rhegmatogenous retinal detachment, proliferative vitreoretinopathy, and inherited retinal disorders. Finally, we discussed DAMPs as biomarkers, therapeutic targets, and therapeutic agents for retinal disorders.

Hyperoside mitigates photoreceptor degeneration in part by targeting cGAS and suppressing DNA-induced microglial activation

“…Damage-associated molecular patterns (DAMPs) are important neuroinflammatory mediators linking dying neurons and activated microglia during retinal degeneration [ 15 ]. Of note, accumulating evidence has supported the important contribution of cGAS-STING pathway in sensing self-DNA, a type of DAMPs, and relaying a cascade of signaling events that eventually lead to microglial activation-mediated neuroinflammation [ 16 , 17 ].…”

“…For instance, cGAS gain-of-function alone is sufficient to drive the pro-inflammatory activation of microglia and promote ageing-associated decline of the neuronal functions [ 16 ]. It has been recognized that stressed or dying photoreceptors release various kinds of DAMPs that may engage in the pro-inflammatory activation of microglia through multiple mechanisms [ 15 ]. In this study, we present new morphological evidence indicating that photoreceptor-derived self DNA is a type of DAMP released early in the photoreceptor degenerative process.…”

Current Treatments and Innovations in Diabetic Retinopathy and Diabetic Macular Edema

“…Another area of research is the role of damage-associated molecular patterns (DAMPs) which are endogenous danger molecules released from the extracellular and intracellular space of damaged tissue or dead cells. These molecules are expressed in different eye diseases, and diabetic retinopathy; the predominant DAMPs are S100, HMGB1, uric acid, HSPs, ATP, cyclophilin A, Aβ, IL 1-α, IL-33, nuclear DNA, mtROS, formyl peptide, and lipid from the mitochondrial membrane [ 92 ]. DAMPs can act on the RAGE, activating the NFκ-β pathway, and activating the transcription of cytokines, chemokines, and other inflammatory mediators involved in DR.…”

Various forms of programmed cell death, including apoptosis and regulated necrosis, are concurrently activated in retinal ganglion cells after ischemia and reperfusion

“…From an immunological perspective, apoptosis is an anti-in ammatory form of cell death, while the release of endogenous factors (proteins, RNA, DNA, etc. ; known as damage-associated molecular patterns or DAMPs) from cells that have lost membrane integrity triggers a strong cytotoxic pro-in ammatory response such as in the case of necrosis (Fadok et Mahaling et al, 2022). Therefore, necrotic programmed cell death can trigger further RGC death after IR (secondary injury).…”