The immune system reacts to damaged and dying cells, as well as their debris. As the level of tissue damage rises with age, this pattern recognition contributes to increasing levels of chronic inflammation. That in turn causes further harm, changing cell behavior for the worse, degrading tissue structure and function.
Inflammation in aging is an example of a process that is beneficial in the short term becoming harmful when sustained for the long term, a process that is beneficial in the youthful environment becoming actively harmful in the age-damaged environment.
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Damage-associated molecular patterns (DAMPs) are endogenous danger molecules released from the extracellular and intracellular space of the damaged tissue or dead cells. DAMPs are (i) rapidly released following necrosis; (ii) produced by the activated immune cells via specialized secretion systems or by the endoplasmic reticulum (ER)–Golgi apparatus secretion pathway; (iii) known to activate the innate immune system by interacting with pattern-recognition receptors (PRRs), and thereby directly or indirectly promote adaptive immunity responses; (iv) inclined to contribute to the host's defense and pathological inflammatory responses in non-infectious diseases; and (v) responsible for restoring homeostasis by promoting the reconstruction of the tissue.
Accumulating evidence indicates that DAMPs are associated with the sterile inflammation caused by aging, increased ocular pressure, hyperglycemia, oxidative stress, ischemia, mechanical trauma, stress, environmental condition, and genetic defects during retinal development. Recent studies suggested that DAMPs that include extracellular matrix (ECM)-proteins are increased; this suggests a protective or pathogenic role in different retinal disorders. In retinal disorders DAMPs function through multiple specialized innate immune receptors, such as receptors for advanced glycation end products (RAGE), toll-like receptors (TLRs), and the NOD-like receptor (NLRs) family.
The diverse nature of the retinal cell types and their neuronal circuitry complicates our understanding of the cell-specific immune responses and the release of DAMPs in various retinal disorders. Therefore, future studies are warranted to identify the DAMPs involved in the molecular mechanisms of retinal diseases, employing single-cell or cell-specific proteomic signatures to identify/design or repurpose next generation therapeutics for retinal disorders.
Link: https://doi.org/10.3390/ijms23052591
Source: Fight Aging!