Development of a New Therapy for Age-Related Macular Degeneration

Marcelo Nociari, PhD
Joan and Sanford I. Weill Medical College of Cornell University (New York, NY)

Co-Principal Investigators

Enrique Rodriguez Boulan, MD
Joan and Sanford I. Weill Medical College of Cornell University
Year Awarded:
Grant Duration:
July 1, 2013 to June 30, 2015
Macular Degeneration
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern

This grant is made possible by a bequest from the Lottie Kubiak Living Trust.

Marcelo Nociari, PhD

Removal of Lipofuscin Bisretinoids from RPE by β-cyclodextrins


With age, our eyes accumulate waste in retinal pigment epithelium (RPE), which supports the life and function of photoreceptors (light sensitive cells in the eye); in advanced stages, RPE and photoreceptors die. In some genetic forms of blindness, this waste accumulates much faster in RPE, resulting in blindness by age 30. Drs. Nociari and Boulan have discovered drugs that remove this waste from RPE. The team proposes experiments to develop strategies to make waste removal more efficient. They expect that this will result in useful drugs to treat human blinding diseases, including dry age-related macular degeneration (AMD).


This proposal provides an outstanding opportunity to develop a novel small drug therapy to preserve and improve retinal function in individuals with dry AMD.

Vitamin A is central for the visual process.  However, during aging the retina accumulates large amounts of toxic waste material derived from vitamin A,; this toxic waste is often referred to as bisretinoid-lipofuscin.  Elevated levels of bisretinoid-lipofuscin have been implicated in AMD progression.  Currently, there is no treatment for the majority of patients with dry AMD and other inherited forms of dry macular degeneration that result from the accumulation of bisretinoids. Hence, agents that efficiently remove bisretinoid-lipofuscin would be extremely valuable therapeutic candidates for treatment of dry AMD.  

Recently, Drs. Nociari and Boulan have identified a family of cyclic sugars, called beta-cyclodextrins (beta-CDs), that bind and reduce bisretinoid-lipofuscin levels from cultured cells. Their data indicate that beta-CDs act by stimulating the degradation of bisretinoid-lipofuscin rather than by expelling it from cells.  In order to maximize the removal potency of the CD treatment, they plan to identify drugs that act synergistically with beta-CDs to augment the degradation of lipofuscin.  They will then test in vivo (in animals) their combination of drugs on the best mouse model available to study lipofuscin-mediated retinal degeneration. After several years of lipofuscin research, this group is in a great position to complete these experiments.  The results of this study will help to fulfill a very much overdue medical need, i.e. the treatment of patients with dry AMD. Since beta-CDs are currently being tested in humans for the treatment of genetic forms of cholesterol accumulation (e.g. Nieman-Pick disease), a successful result in this study might mean that the drug combination could then be accelerated for testing in clinical trials for AMD. 

About the Researcher

Dr. Marcelo Nociari is an assistant research professor of ophthalmology at the Dyson Research Institute at Cornell University. He earned a BA in Chemistry, a BS in Biochemistry and a PhD in immunology from the University of Buenos Aires. In 1996, he arrived to the U.S to pursue postdoctoral studies in aging and innate immunity. Dr. Nociari’s research team is deeply interested in developing new drugs to reduce the accumulation of lipofuscin-bisretinoids in the retina and to control the chronic inflammation consistently associated with AMD. Dr. Nociari uses animal models, cell culture, and clinical approaches to study from different perspectives the impact that lipofuscin accumulation has in retinal disease. In addition to the BrightFocus award, Dr. Nociari has received a number of grants from NIH.

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