Inflammation and oxidative stress in retinal diseases: the role of intracellular signaling in the retinal pigment epithelium

Abstract

The retinal pigment epithelium (RPE) is essential for the integrity and function of the retina. RPE cells exert key functions to maintain photoreceptors´ (PRs) viability and functionality, such as light absorption and protection against photo-oxidation, phagocytosis of photoreceptor outer segments (POS), transport of nutrients and water, secretion of several growth factors and reisomerization of all-trans-retinal. The RPE is also part of the outer blood-retinal barrier (BRB) and can secrete immunomodulatory molecules. This review summarizes signaling events elicited in RPE cells under stress conditions, such as bacterial endophthalmitis, hyperglycemia and oxidative stress (OS). Inflammation and OS participate in the pathogenesis of several retinal diseases that eventually end in vision loss and blindness, such as age-related macular degeneration (AMD),diabetic retinopathy (DR), retinitis pigmentosa and uveitis. Elucidating the molecular events involved in the inflammatory process in the RPE could thus lead to the discovery of new therapeutic targets for the treatment of retinal degenerative diseases. RPE response to inflammatory situations can mediate retinal damage or survival depending on the inflammatory context and stress duration. Independently of the nature of the stress inductor, intracellular events involved in RPE cell damage could be postulated as therapeutic targets for the treatment of ocular inflammatory diseases, among them: extracellular signal-regulated kinase (ERK) as well as the nuclear transcription factor-κB (NF-κB) activation and increased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression.