Nicotinamide as a treatment option of Age-Related Macular Degeneration

Abstract

Age related macular degeneration is a severe disease of mainly elderly people and leads to central vision loss because of the degeneration of the retinal pigment epithelium [1]. Genetic and environmental factors are responsible for the accumulation of extracellular material and deposit formation near the retinal pigment epithelial (RPE) layer, which leads to loss of photoreceptors and induction of chronic in lammation. The deposits are composed of lipids and proteins including many complement proteins, indicating the involvement of the complement system in the degenerative process and chronic in lammation [2]. So far there is no treatment for the dry form of AMD, except nutritional supplementation with antioxidants and vitamins [3]. Combined with a prolonged lifetime expectation in developed countries, AMD is developing to a social and economic burden. Therefore, there is an urgent need for a treatment of AMD that can delay disease manifestation and progression for several years.In a recent manuscript, Saini and colleagues analyzed a vitamin B derivate, nicotinamide (NAM), as a potential treatment strategy of AMD [4]. The antiin lammatory activity of NAM is not entirely new and may have inspired the investigators to look in detail at the effect of this drug for AMD treatment. In 2008, Temple and her group reported about the treatment of 3 x Tg-AD mice, a mouse model for Alzheimer's disease (AD), with NAM. Their work suggested that NAM treatment selectively reduces a phosphorylated species of tau associated with microtubule depolymerization and implicated in AD. Treatment of mice restored cognitive decline related to AD pathology indicate a readily available therapeutic for the treatment [5]. Collectively NAM was identi ied as a cytoprotectant that blocks cellular in lammatory cell activation, early apoptotic phosphatidylserine exposure, and late nuclear DNA degradation [6]. Therefore, NAM supplementation was suggested for the treatment of chronic diseases with an immune system dysfunction as seen in diabetes and agerelated diseases.Sinai et al. [4], investigated the effects of NAM in a human induced pluripotent stem cell (iPSC) model of AMD which they they previously established. The advantage of this model is evident. The investigators used cells from AMD patients with or without a speci ic ARMS2/HTRA1 risks haplotype as well as from control people to generate iPSCs and to compare the effects of NAM. The authors showed that iPSC cells express a broad panel of drusen like deposits and AMD associated molecules. Also, iPSC-RPE from all AMD patients studied, demonstrated an increased expression of in lammatory and complement factors as compared to controls. The expression of complement genes C3 and CFI was signi icantly enhanced in patient cell lines carrying the homozygous