Eyeworld

EW RETINA 128 March 2017 noticeable functional changes. This is something that's preceding the retinal degeneration and function and could indeed be a viable thera- peutic target." The idea is that NAD+ levels could someday be used as a diag- nostic tool or alert to the need for therapy before visual function is im- paired. This, however, is still a long way off, said Rajendra Apte, MD, you could delete a single enzyme in this one pathway and actually cause complete degeneration and impair retinal function." The measurable reduction in NAD+ at 3 weeks, followed by functional deficits by 6 weeks, is significant. "At that point, there is still a relatively intact photoreceptor layer and some measurable retinal function. It does seem that NAD+ deficiency is preceding the degener- ation," Mr. Lin said. "Further we've looked at a few different mouse dis- ease models, including a chemically induced diabetic retinopathy model … and a light-induced degeneration model, and we also looked at aging as a process. In all of these cases, we actually observed retinal NAD+ deficiency that occurred prior to PhD, Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences, Washington Univer- sity School of Medicine, in whose lab the studies were conducted. "Right now you can potentially do systemic testing to see what the NAD+ levels are in the rest of the body and indirectly conclude about [NAD+ levels in the retina,]" Dr. Apte said. "But it's a little compli- cated to do—it's more of a research tool—but you can see down the road how that could provide more insight into maybe people who are more susceptible than others." As for rescuing at-risk cells be- fore they're actually damaged or lose function, the study demonstrated that administration of nicotinamide mononucleotide (NMN)—an NAD+ precursor—in mice lacking the gene to drive the NAD+ pathway prevent- ed vision loss. "NMN is the downstream product of the enzyme we knocked out," Mr. Lin explained. "It makes sense that if you're knocking out this pathway, that in order for you to rescue it, you have to bypass it. That's what NMN can do." Dr. Apte said that clinical trials using different NAD+ metabolites, such as nicotinamide riboside, are already taking place to establish safe- ty and efficacy of the compounds increase NAD+ 2. A phase 1 clinical trial using NMN on healthy people began in 2016 at Keio University School of Medicine, Tokyo, Japan, and U.S. trials will begin in spring 2017. "We're making good progress in trying to see if there are any effects modifying this pathway," Dr. Apte said. "In the best case scenario, if something like this becomes a drug, then we will have treatment options that will compliment what we have now for things like macular degen- eration [and also] maybe therapies for which there are very few options available, like some of the retinal degeneration diseases." EW References 1. Lin, J, et al. NAMPT-mediated NAD+ bio- synthesis is essential for vision in mice. Cell Reports. 2016;17:69–85. 2. Trammell, S, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016;7. E-pub. Editors' note: Dr. Apte and Mr. Lin do not have financial interests related to their comments. Contact information Apte: apte@wustl.edu Lin: jblin@wustl.edu Join the largest subspecialty society representing the fields of cornea and external disease. Member Benefits • Cornea: The Journal of Cornea and External Disease • Annual Meetings: Select discounted registration at membership events and educational programs • VideoEd: A weekly broadcast of clinical videos recorded live at national and international meetings • Kera-net: The online forum for the exchange of clinical and scientific information • Cornea Society News: Quarterly newsletter sent to all Society Members www.CorneaSociety.org Researchers continued from page 126

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