Microglial alterations as a possible treatment target in retinitis pigmentosa

Abstract

AbstractPurpose: The term retinitis pigmentosa (RP) describes a group of hereditary retinopathies. The first clinical signs of RP are night blindness and loss of peripheral vision. Central vision remains preserved until advanced stages of the disease. At a cellular level, the rods are the first to degenerate. Subsequently, there is degeneration of the cones. Inflammation plays a fundamental role in RP. The microglia respond quickly to alterations, acquiring amoeboid morphology; migrating to damage focus; acquiring macrophages functions; phagocytosing cellular debris; secreting molecules that initiate tissue repair; and favouring neuroprotection. However, if the activation is excessive, the constant secretion of nitric oxide and proinflammatory cytokines lead to pathological side effects. The purpose of this work was to review published studies in order to know if the inhibition of micloglial activation may be a good option to increase photoreceptor protection.Methods: A systematic literature review was conducted, in accordance with PRISMA criteria, in different bibliographic databases: Medline, Embase, SCOPUS and Web of Science. We searched human and animal reviews, published in English in the past 10 years. Initial search terms were ‘retina’, ‘retinitis pigmentosa’, ‘retinal degeneration’ and ‘therapeutics. Duplicate studies were removed, and the remaining articles were assessed for eligibility by full‐text review.Results: Understanding the mechanisms leading to photoreceptor death is essential for the development of new treatments in RP. It has been shown increased retinal infiltration of activated microglia in many animal models of RP. Different works have studied the clinical efficacy of antioxidants, minocycline, transforming growth factor beta or tamoxifen. However, the complete efficacy in RP has not been fully established.Conclusions: Pharmacological inhibition of microglial activation may be a good therapeutic target to reduce photoreceptor cell death in RP.