**4. RPE and immune response in neovascular AMD**

There are multiple pathways by which the RPE can regulate the retinal immunelandscape, which in turn can regulate neovascularization in AMD:


**137**

**8. Genetics**

*Introductory Chapter: Macular Degeneration: Mechanisms of Action*

immunopathology of CNV will require an assessment of all potential vascularmodifying immune cells and their subsets, in health, disease, and following

Toxic accumulations, either within the RPE cell or at the RPE-Bruch membrane interface, are the molecular hallmarks of dry AMD [18]. Dry AMD may be considered as a form of a metabolic storage disease; two approaches to preventing their formation or removing them after formation are attempts to prevent RPE damage. AMD and other neurodegenerative disorders occur when a particular cell or group of cells die. In this scenario, AMD might share some pathogenetic mechanisms with several common neurodegenerative diseases of aging, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease in which mitochondrial defects, DNA mutations, impaired structural integrity, and defective mitochondrial function. Other toxins accumulate in AMD; an excessive amount of "lipofuscin," which is nondegradable debris that accumulates in the RPE with age, is associated with AMD. In the

presence of light, lipofuscin forms ROS and is toxic to RPE cells [19–20].

Cells are equipped with machinery to discard toxic accumulations with a self-cleansing process called macroautophagy. Autophagy of the mitochondria and other cellular debris could rejuvenate cells by disposing defunct organelles, a concept which has been reviewed for AMD. Autophagy may also regulate RPE health by reducing cytotoxicity that is secondary to a primary insult. Future work should address several basic questions about this cell survival mechanism in AMD [21–23].

Smoking of cigarette confers the greatest numerical risk for AMD with two to three times likely than nonsmokers to develop AMD (smoking cessation reduces the risk of developing AMD) [24]. Several nutritional deficiencies are associated with AMD risk. In a recent epidemiologic study, omega-3 fatty acid (FA) intake was associated with a lower risk of AMD [25]. The protective effect of statins on AMD is not well established and would require long-term prospective interventional studies

One prevailing approach in AMD research was the genome-wide association studies (GWAS) that have been used in attempt to predict risk of disease, understand pathogenesis, and identify potential therapeutic target [26]. GWAS have indeed identified several genetic loci, which harbor genetic variants known as single nucleotide polymorphisms (SNPs) that are associated with an increased risk of AMD. Factor H (CFH) represents the complement gene variant conferring the greatest quantitative statistical AMD risk. CFH inhibits a key activation step in complement activation, thereby reducing complement-induced host cell damage and inflammation [27]. The predictive power of AMD risk assessment can be

*DOI: http://dx.doi.org/10.5772/intechopen.86739*

therapeutic intervention [17].

**6. Autophagy and damage control**

**7. Environmental risk factors**

to confirm its relevance to AMD pathogenesis.

**5. Dry AMD**

immunopathology of CNV will require an assessment of all potential vascularmodifying immune cells and their subsets, in health, disease, and following therapeutic intervention [17].
