An alternate approach is to identify treatment regimens that work via multiple or less specific mechanisms. Metanx is a prescription medical food product that contains
l-methylfolate, pyridoxal 5′-phosphate, and methylcobalamin, which are the active forms of vitamins B
9, B
6, and B
12. The active metabolite of folate,
l-methylfolate, is known to stabilize and enhance production of tetrahydrobiopterin, a cofactor of iNOS, which inhibits uncoupling and associated superoxide generation.
9,10 Methylcobalamin (a coenzyme form of vitamin B
12) reacts with superoxide and inhibits glutathione depletion and peroxynitrite generation.
11 Pyridoxal phosphate has been reported to inhibit formation of advanced glycation end products (AGE), act as a metal chelator, and show antioxidant properties in diabetes
12 and has been studied as a potential treatment for neuropathy in diabetes and other conditions.
13–19 Consistent with these separate effects, Metanx has been reported to have beneficial effects on endothelial dysfunction and on peripheral nerves in diabetic rodents and patients.
15,16,18,19 Thus, Metanx therapy has shown effects that might be beneficial for diabetic retinopathy. A pilot clinical trial in which Metanx was administered daily as an intervention for 6 months to 7 patients with early to intermediate diabetic retinopathy
20 reportedly had statistically significant but modest effects on diabetes-induced alterations of retinal threshold sensitivity or central retinal thickness. Whether administration of this therapy for a longer duration or administration from the onset of diabetes would have had more favorable effects is not clear. In the present study, we evaluated the effects of Metanx on the development of diabetes-induced alterations in retinal physiology, inflammation, histopathology, and visual function in mice.