Age-related macular degeneration (ARMD) is the leading cause of severe vision loss and blindness worldwide, mainly affecting people over 65 years old. Dry and wet ARDM are the main types of the disease, which seem to have a multifactorial background. The aim of this review is to summarize the mechanisms of ARMD pathogenesis and exhibit the role of diet and nutritional supplements in the onset and progression of the disease. Environmental factors, such as smoking, alcohol, and, diet appear to interact with mutations in nuclear and mitochondrial DNA, contributing to the pathogenesis of ARMD. Inflammatory mediators and oxidative stress, induced by the daily exposure of retina to high pressure of oxygen and light radiation, have been also associated with ARMD lesions. Other than medical and surgical therapies, nutritional supplements hold a significant role in the prevention and treatment of ARMD, eliminating the progression of macular degeneration.
Age-related macular degeneration (ARMD) is the leading cause of severe vision loss and blindness worldwide, given that its incidence ranges from 9 to 25% at ages between 65 and 75 years, leading to blindness of over 80% of affected patients after the age of 70 years [
The retina is responsible for the conversion of light stimuli to neural impulses, which are transmitted to the visual cortex (occipital lobe). It consists of an outer pigmented layer (retinal pigment epithelium, RPE), which lays on Bruch membrane and an inner sensorineural layer (sensory retina), including the photoreceptors which transmit the electrical stimulus to nerve fibers layer, forming the optical nerve [
Drusen are located between the RPE and Bruch’s membrane of the macula or the peripheral retina and they mainly consist of phospholipids, triglycerides, cholesterol, cholesteryl esters, apolipoproteins, vitronectin, immunoglobulins, amyloid, and complement system components (Figure
Hard drusen at the temporal side of macula in patient with dry ARMD (a), geographic atrophy (b), and CNV in patient with wet ARMD (c).
The pathogenesis of ARMD is multifactorial, related to environmental factors, genetic background, and parainflammation. Smoking is considered to be a major risk factor for the onset and the progression of ARMD, which has been positively correlated with the duration of smoking and the number of cigarettes [
High levels in serum of apolipoprotein B were related to inflammation and accumulation of drusen in the retina of patients suffering from wet ARMD [
Single-nucleotide polymorphisms (SNPs), mutations of mitochondrial DNA (mtDNA), and micro-RNAs (mi-RNAs) consist of the genetic background of ARMD. Polymorphisms of complement factor (CF) I (CFI, chromosome 1q32), C3 complement component (chromosome 19p13), CFV, and C2 complement component (chromosome 6p21), as well as ARMS2/HTRA1 (chromosome 10q26) genes, are primarily related to the incidence of AMRD in the western world [
The presence of any harmful agent results in activation of parainflammation, which aims at homeostasis and normal tissue function. Prolongation of parainflammation leads to oxidative stress and degenerative processes, associated with diseases such as atherosclerosis, diabetes mellitus, and ARMD [
Studies in aged RPE revealed high levels of VEGF and interleukins (IL) 12 and 10, although both of these interleukins exhibit inverse effect, since the former promotes the production of interferon gamma, TNF-a, and T-lymphocytes, while the latter inhibits inflammatory mediators [
Although lipofuscin is normally found in retinal epithelium, extremely elevated concentrations of this pigment have been associated with cell damage, induced by the formation of CEP proteins (carboxyethylpyrrole proteins) and bis-retinoids oxidation [
PAF (1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a low molecular weight phospholipid, regulated by PAF acetylhydrolases (PAF-AHs), a group of phospholipases being responsible for hydrolysis and deactivation of PAF in blood and tissues, as well as by its receptor (PAF-R, flt-1), which is a transmembrane G-protein, being expressed in a wide range of cells (RPE cells, monocytes, lymphocytes, vascular endothelial and smooth muscle cells, and keratinocytes) [
Allergic conjunctivitis has been related to release of histamine and serotonin, vasodilation, increased vascular permeability and accumulation and degranulation of eosinophils, and neutrophils, caused by the ocular action of PAF [
Food supplements appear to be the basic therapy of dry ARMD, whereas exudative form is treated with the use of anti-VEGF and anti-inflammatory agents, as well as laser (laser photocoagulation or photodynamic therapy). Ranibizumab (Lucentis; Genentech, South San Francisco, CA/Roche, Basel, Switzerland, 2006), bevacizumab (Avastin; Genentech, South San Francisco, CA/Roche, Basel, Switzerland, 2005), pegaptanib sodium (Macugen; Eyetech Inc., Palm Beach Gardens, FL, 2004), and VEGF trap or Aflibercept (EYLEA; Regeneron Pharmaceutical Inc. and Bayer, Tarrytown, NY, 2011) are the major anti-VEGF agents used in treatment of wet ARMD [
AREDS study, conducted with 4757 participants aged 55–80 years, revealed that the daily intake of zinc (80 mg), copper (2 mg), and antioxidants (vitamin C: 500 mg, vitamin E: 400 IU, beta-carotene: 15 mg) reduces the risk of advanced ARMD lesions (OR: 0.75 and decrease of relative risk (RR) by 21% for an individual taking zinc, OR: 0.80 and RR reduction by 17% for individuals taking antioxidant components), preventing visual loss (OR: 0.72 and RR reduction by 25%) [
The effect of vitamin supplements on the action and metabolism of PAF was recently investigated in rabbit’s platelets and leucocytes. All supplements, including InShape (Farmex), Nutrof (Thea), Ocuvite (Bausch and Lomb), and Vitalux (Novartis), appeared to inhibit, even in low dose, the aggregation of platelets, which is closely related to the action of PAF [
The multifactorial background of ARMD complicates the treatment of the disease and generates the need for continuous research in ARMD therapy, taking into account that 80% of affected patients are blind after the age of 70 years. Numerous studies have highlighted the role of diet and vitamin supplements in inhibiting parainflammation and oxidative stress, which are involved in pathogenesis of ARMD. Changing dietary habits and eliminating smoking and alcohol could prevent the onset and the progression of ARMD, protecting the patients from vision loss and blindness.
The authors declare that there is no conflict of interests regarding the publication of this paper. The authors alone are responsible for the content and writing of the paper.