*5.3. Age-Related Macular Degeneration*

AMD is a leading cause of worldwide blindness in the elderly population, a ffecting 200 million individuals by 2020 and nearly 300 million by 2040 [134]. The pathological aging of the macula can cause dry or non-neovascular and wet or neovascular AMD. At the early stage, accumulation of extracellular material forms drusen between the basal lamina of the RPE and the inner layer of Bruch's membrane in the eye. At the late stages, degeneration of the PR overlying the drusen can cause severe central vision loss in the dry form, whilst formation of new abnormal blood vessels from the choroid growing into the retina can cause subretinal fluid accumulation and bleeding. The wet form progresses rapidly and is responsible for 90% of severe vision loss associated with AMD. The pathogenesis of AMD is multifactorial, with genetic and environmental factors such as smoking. It is associated with dysregulations in the angiogenic, oxidative stress, lipid, inflammatory, and complement pathways [135]. Patients with early AMD have more iron in the macula than healthy patients. Iron deposits are found in the melanosomes of the choroid and the RPE, in the central layer of the calcified Bruch's membrane, in the drusen, and at the level of the PR [136]. Part of this iron, found in the pathological retina of AMD patients, is in the toxic free form [137]. Patients with dry AMD have more than twice the concentration of iron in their aqueous humor than in patients with cataract surgery [138]. The macular region of AMD patients with geographic atrophy showed an increase in the expression of proteins involved in iron homeostasis such as TF, FT, and FPN in the PR layer and feet MGC [139]. TF and CP mRNAs

are increased in the two advanced forms of AMD [140]. In the serum of patients with the di fferent forms of AMD, a significant increase in TF and TFR1 and a significant decrease in the concentration of soluble FT were observed while iron levels were unchanged [141]. Several polymorphisms of the iron homeostasis genes have been associated with risk factors for AMD: *Tfr1*, *Tfr2* (obesity, tobacco) [142], *Dmt1* [143], *Irp1* and *Irp2* [143], and *heme oxygenases 1* and *2* (HO1/2) [144]. A recent study has shown that the expression of several miRNA, small non-coding RNA molecules binding in 3'UTR genes, was modified in the serum of AMD patients, especially those controlling the translation of the TFR1 and DMT1 proteins [145].
