Biomarkers for Inflammation May Help Identify Risk for AMD
The development of effective and preventative therapies for age-related macular degeneration (AMD) may be linked to the metabolism of homocysteine (Hcy), according to new research published in Medical Hypothesis.
Majavir Singh, DVM, PhD, and Surech C Tyagi, PhD, of the University of Louisvile School of Medicine, propose that "Hcy makes a greater contribution to the overall etiology of AMD disease" by "inciting and accelerating the inherent inflammatory changes in the retina of these patients." It should be considered as an important biomarker of retinal diseases, they added.
Homocysteine is a biosynthesized amino acid which assists cysteine in creating protein, but when Hcy metabolism is unbalanced, it can lead to increased levels of Hcy that can sometimes lead to hyperhomocysteinemia, which are connected with blood clots and arthrosclerosis.
Additionally, hyperhomocysteinemia (HHcy), a known risk factor for vascular diseases, can lead to increased risk of damage to endothelial cells and vascular inflammation. It is the inflammatory effects of Hcy that are particularly concerning, Singh and Tyagi emphasized.
According to their proposal, the degenerative changes of AMD can be affected by Hcy, and the pair "strongly believe that defining a new marker of AMD such as Hcy may provide further additional insights into the overall pathology of the disease process" for both wet and dry AMD. Hcy levels are known to increase with age where they may "upregulate" inflammatory cytokines and chemokines.
Hcy has also, Singh and Tyagi state, "been suggested as a powerful physiological stressor in the eyes where it generates lens oxidation," degrades proteins, and plays a role in the decline of antioxidant defense mechanisms associated with cataracts.
The authors explain that although HHcy has been reported in patients with AMD, there has been little research done to examine whether Hcy serves as an inflammatory modulator, or what role elevated Hcy in patients with AMD may play in disease risk or progression.
The researchers point out that Hcy may have a very complex relationship to AMD and other optic atrophy disorders, which suggests that HHcy could act as an "initial trigger for the inflammatory process," leading to pathological changes in the eye and degeneration of the macula.
"Because macula receives the highest blood supply of any tissue in our body when related to size," the authors wrote, anything that "reduces the blood supply can cause hypoxia, and tissue malfunctioning."
The inflammatory effects of HHcy could certainly lead to vascular damage in the macula, according to the authors, and elevated Hcy levels may help identify risk factors for AMD.
The pair's hypothesis is based on their research on elevated Hcy levels relationship to cytokine and chemokine inflammation associated with retinal cells, chronic kidney disease, and chronic metabolic disorders.
Elevated Hcy, folate and vitamin B-12 deficiencies predict an increased risk of AMD, the paper said, and therapeutic interventions which focus on decreasing Hcy levels have helped slow down worsening eyesight in a subset of patients.
Hcy elevation, the researchers argue, could be an underlying factor driving AMD. Because AMD affects so many millions of people globally, Singh and Tyagi recommend that the role of Hcy in AMD development become a focus for study. Determining the nature of links between Hcy and AMD could lead to breakthrough preventative and treatment therapies.
The article "Hyperhomocysteinemia and age-related macular degeneration: Role of inflammatory mediators in disease pathogenesis; A proposal" appears in the August 2017 issue of Medical Hypothesis.
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