**1. Introduction**

Age-related macular degeneration (AMD) is an idiopathic degenerative disease of the retina and the cause of irreversible and profound vision loss in people older than 60 years [1]. Because of the rapidly aging population, it is easy to predict a worldwide increase in the incidence of AMD, resulting in increased costs on healthcare services. AMD presents in two main forms: Dry-AMD and Wet-AMD. Dry-AMD is characterized by atrophy of retinal pigment epithelial (RPE) cells and degeneration of adjacent photoreceptors. This form of the disease accounts for approximately 25% of cases, and patients experience severe loss of central vision. In contrast, wet-AMD is characterized by the formation at the level of the choroid of new vessels (CNVs) that branch out to the outer layers of Bruch's membrane, located beneath the basal membrane of the RPE, or across the RPE into the subretinal space. These vessels are usually constituted by a fragile endothelium and therefore subject to injury with subsequent hemorrhage and macular neuroretinal detachment. This form accounts for 75% of cases with severe central vision loss [2]. Despite their different pathophysiology and symptomatology, the two forms of AMD share similar risk factors for their development.

AMD is an aging-related syndrome caused by multiple factors including environmental, nutritional, and behavioral [3, 4] as well as genetic background can make an individual more or less susceptible to these factors [4, 5]. As in most diseases affecting the outer retina, loss of visual function in AMD results from degeneration and death of photoreceptors in the central retina, but in the initial pathogenesis of dry

AMD, the involvement of RPE cells [6] has been studied. The specific genetic and biochemical mechanisms responsible for RPE degeneration in AMD are still under investigation, but recent advances in understanding dry AMD suggest that oxidative stress and inflammation may be two of the cellular mechanisms underlying RPE cell death with an important role in drusen biogenesis and perhaps in the etiology of AMD in general [7, 8].

The RPE is a monolayer of cuboidal cells subjacent to the neural retina [9]. The basal cell membrane of the RPE is in contact with Bruch's membrane, a multilayered matrix that separates the RPE from the underlying choroidal vasculature. The apical membrane of the RPE is intimately interdigitated to the outer segments of the underlying photoreceptors. The main function of the RPE, which forms a part of the blood-retinal barrier, is to support the survival and normal function of the photoreceptors, in fact it controls the exchange of nutrients, waste products, ions, and gases between the choroidal blood vessels and the photoreceptors [10]; RPE is involved in the transport of retinol necessary for the synthesis of the visual pigment of photoreceptors [11] and in the phagocytosis of photoreceptor outer segment membrane disks (POS) [12]. In addition, RPE cells produce trophic and immunological factors necessary for the survival and protection of photoreceptors and the entire eye [13].

In addition to oxidative stress and inflammation, triggered by multifactorial events, infection by pathogens may also be a cause of damage and degeneration of RPE cells [14] and eventually lead to the onset of AMD.
