The RPE Cell and the Immune System

The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies

“…The retina is equipped with a highly sensitive innate immune system that responds with three key pathways: migration of microglia cells, activation of the complement system to opsonize cellular debris, and inflammasome assembly in the RPE (reviewed in [20]). To achieve this coordinated response, retinal cells express a panoply of immune protein receptors and mediators such as, microbial sensors (Toll-like receptors-TLRs), NOD-like receptors-NLRs, RIG-1 like helicases), cytokines, chemokines, as well as a group of complement components; all directed to assist the cells with eliminating the current insult [21]. In oxidative stress conditions, rapid activation of this immune response is intended to induce restoration of tissue homeostasis, but upon persistent damage, chronic overactivation of the inflammatory response can cause devastating tissue remodeling and destruction, thus leading to irreversible retinal pathologies, such as age-related macular degeneration (AMD) or diabetic retinopathy (DR).…”

“…In fact, these pro-inflammatory cytokines are upregulated in the eyes of patients suffering glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, or retinal vein occlusion. Particularly, endothelial cells affected by inflammation show phenotypic changes due to the increase of the expression of inflammatory mediators and cytokines as well as iNOS activation [21].…”

“…Microglia cells are resident retinal macrophages that confer neuroprotection against ROS damage and other injuries. In healthy retinas, microglial cells phagocyte accumulated waste products and cellular debris but under oxidative stress, hypoxia, or inherited mutations, NFκB-mediated inflammatory responses are activated, and microglial cells acquire amoeboid morphology, proliferate, and migrate to the sites of injury, as deteted by Iba-1 positive cells in the photoreceptor layer [21,22]. Oxidative stress promotes the degradation of sialic acid residues of membrane proteins, leaving photoreceptors and other cells with a damaged glycocalyx, and leading to enhanced phagocytosis by microglial cells, and increasing neuronal cell death, which worsens the pathology.…”

“…These free radicals are generated from glucose auto-oxidation reactions and glycated adducts of proteins. These metabolic changes increase the levels of pro-inflammatory cytokines, chemokines and other mediators of the inflammatory response stimulating an influx of leucocytes and altering vascular permeability, which altogether favors the degeneration of the retina [21,26,61,94].…”

Antioxidant and Biological Properties of Mesenchymal Cells Used for Therapy in Retinitis Pigmentosa

“…Their activation involves the expression of inflammatory regulatory proteins such as peroxiredoxin 2 (PRDX2), pro-inflammatory cytokines such as TNF-α, interleukin-1β or interferon-γ in RPE cells [ 90 , 91 ], chemokines and neurotoxic agents, including hydrogen peroxide, and superoxide anion with additional oxidative stress [ 92 , 93 ].…”