A New Therapeutic Strategy to Treat AMD

Sabrina Carrella, PhD Telethon Institute of Genetics and Medicine (TIGEM)-Fondazione Telethon

Co-Principal Investigators

Alessia Indrieri, PhD


Age-related Macular Degeneration (AMD) is a common cause of blindness worldwide and the loss of vision is due to progressive loss of specific cell type of the eye important in the visual process. Multiple factors, genetic and environmental factors, are involved in the onset and progression of this disease. We have identified two small non-coding ribonucleic acids (RNAs), called microRNAs that are able to control many fundamental cellular processes and whose inhibition can protect ocular cells from damage and rescue alterations of vision. We propose to test the beneficial effects of the inhibition of these two microRNAs in macular degeneration animal models and pave the way for the set up of a novel therapeutic strategy for this complex disease.

Project Details

The short-term goal of this project is to provide a proof-of-principle for the putative effectiveness of the inhibition of these microRNAs in AMD treatment. We divided the project in three specific aims that will be completed in two years. During the first year we will study the effects of genetic inactivation of the two microRNAs in an AMD-like mouse model that display a lipofuscin-related retinopathy, representing a suitable model for the evaluation of AMD therapeutic strategies in vivo. This strategy will be particularly helpful to test and define the protective effect of the downregulation of microRNAs and the underlying molecular mechanisms in an AMD-like model. During the second year we will evaluate the putative therapeutic effect of inactivation of microRNAs in AMD-like models by using Adeno Associated Viruses (AAV) encoding microRNAs inhibitor molecule, which allow long-term effect in vivo. The in vivo models that will be used mimic AMD environmental risk factors such as oxidative damage from sunlight or cigarette smoking, and present different features of the disease (e.g. progressive visual decline, ‘drusen’-like deposits, disrupted RPE cell junctions), as well as lipofuscin accumulation. MicroRNAs are promising therapeutic tools due to their capability to simultaneously modulate multiple molecular pathways involved in pathogenesis and progression of multifactorial diseases. Their use as therapeutics has been recently applied to different disorders and has reached the preclinical and clinical stages in complex diseases. The modulation of these two microRNAs will provide a broad applicable therapeutic strategy that could be of benefit to a vast number of patients. The proposed workplan will determine the potential application of microRNAs modulation as a therapeutic strategy for AMD. Moreover, our results will provide tools and information necessary for clinical translation of the proposed therapeutic strategy. On the long run, the results generated by the proposed workplan could lead to the design of a novel RNA-based therapeutic product that could readily translated into clinical application in AMD and other form of retinal degeneration.