Hyperhomocysteinemia and Age-related Macular Degeneration: Role of Inflammatory Mediators in Disease Pathogenesis; A Proposal

Publication date: Available online 23 June 2017
Source:Medical Hypotheses
Author(s): Mahavir Singh, Suresh C. Tyagi
Age-related macular degeneration (AMD) causes irreversibly adverse vascular changes in the eyes leading to central vision loss in patients. It is the most common eye disease affecting millions of people aged 50 years or older, and is slowly becoming a major health problem worldwide. The disease mainly affects macula lutea, an oval-shaped pigmented area surrounding fovea near the center of retina, a region responsible for visual acuity. It is fairly a complex disease as genetics of patients, environment as well as risk factors such as age, family history of CVDs, diabetes, gender, obesity, race, hyperopia, iris color, smoking, diabetes, exposure to sunlight, etc. have all been clubbed together as probable causes of macular degeneration. Among genes that are known to play a role include variant polymorphisms in the complement cascade components such as CFH, C2, C3, and CFB as potential genetic risk factors. So far, AMD disease hypothesized theories have not resulted into the anticipated impact towards the development of effective or preventive therapies in order to help alleviate patients' suffering because, as of today, it is still unclear what actually initiates or leads to this dreaded eye condition. Based upon our extensive work on the metabolism of homocysteine (Hcy) in various disease conditions we, therefore, are proposing a novel hypothesis for AMD pathogenesis as we strongly believe that Hcy makes a greater contribution to the overall etiology of AMD disease in a target population of susceptible hosts by inciting and accelerating the inherent inflammatory changes in the retina of these patients (Fig. 2). In this context, we further state that Hcy should be considered as a legitimate and valuable biochemical marker of retinal dysfunctions as it not only aides and abets in the development but also in the progression of AMD in older people as discussed in this paper. This discussion should open up new avenues in tackling immune inflammatory pathway(s) that are upregulated or solely promoted by Hcy interaction within the ocular compartment of AMD susceptible hosts.



http://ift.tt/2t2RuqF