Role of the Light-sensing Photoreceptor Cells in AMD

Claudio Punzo, PhD
University of Massachusetts School of Medicine (Worcester, MA)

Collaborators

Rahul Kanadia, PhD
University of Connecticut (Mansfield, CT)
Year Awarded:
2017
Grant Duration:
July 1, 2017 to August 30, 2019
Disease:
Macular Degeneration
Award Amount:
$160,000
Grant Reference ID:
M2017071
Award Type:
Standard
Award Region:
US Northeastern
Claudio Punzo, PhD

Role of Photoreceptors in AMD

Summary

Age-related macular degeneration (AMD) is one of the leading causes for blindness in the elder population of the industrialized world.  Besides aging of the body, it’s not well understood what causes the disease to occur in a certain percentage of elderly people, which makes it difficult to develop therapeutic strategies.  Based on a new paradigm-shifting idea about how AMD develops, we have generated a new mouse model for the disease that for the first time shows a natural progression of most of the clinical pathologies found in humans, including geographic atrophy and wet AMD.  Our new mouse model of AMD therefore allows us for the first time to study how AMD develops, which will help with the development of new rational therapeutic approaches.

Details

Our hypothesis is that AMD is caused by photoreceptors, more precisely, by age-related metabolic adaptations in photoreceptors. To test this hypothesis we have generated a new mouse model with altered cell metabolism in photoreceptors. This mouse model recapitulates many features of human AMD. The goal of this study is twofold: First, to determine to which extent our new mouse model mimics the human pathology, and second, to identify the metabolic change in photoreceptors that precipitates AMD in our mouse model. In Aim 1, we will focus on the metabolic changes in rod photoreceptors, and in Aim 2, we will focus on those occurring in cone photoreceptors to determine whether the metabolic changes in photoreceptors that cause AMD are the same between the night active rod photoreceptors and the day active cone photoreceptors. The uniqueness of this study is that it proposes a paradigm-shifting view of our understanding of how AMD develops. Putting photoreceptors at the center of AMD’s development allows us to answer many of the unresolved questions regarding this disease. Successful completion of the study will thus redirect research efforts in the field and lay the groundwork for many researchers to identify novel therapeutic targets that can delay disease onset.

About the Researcher

Dr. Claudio Punzo was born in Basel, Switzerland. He received his PhD degree from the University of Basel, working on Drosophila eye development in the laboratory of Dr. Walter J. Gehring. This thesis work addressed the function of the evolutionary conserved transcription factor Pax-6, a master control gene of eye development that contains two DNA-binding domains. Mutations in Pax-6 cause eye abnormalities in humans. Dr. Punzo’s studies have contributed to the understanding of why most of these mutations that cause eye abnormalities in humans are located only in one of the two DNA-binding domains of Pax-6. After completion of his thesis, Dr. Punzo joined the laboratory of Dr. Constance L. Cepko in the Department of Genetics at Harvard Medical School for a post-doctoral fellowship on retinal degeneration. In Dr. Cepko’s laboratory, he initiated a new line of research based on his interests in retinal degeneration, specifically retinitis pigmentosa. Retinitis pigmentosa is an inherited disorder that affects cone and rod photoreceptors, leading to progressive vision loss. Interestingly, most mutations that cause retinitis pigmentosa are in genes that are exclusively expressed in rods, however, cones die too. Dr. Punzo's studies on retinitis pigmentosa led to the proposal of a new model that explains why cones depend on rods for their survival. In 2010, Dr. Punzo joined the Ophthalmology Department at the University of Massachusetts Medical School as an assistant professor to continue to work on retinitis pigmentosa and to lead his own independent research group. Recently, Dr. Punzo has expanded his research interests into the field of AMD, a disease he believes may be caused by photoreceptors. (For updates on his research visit Dr. Punzo's website at: http://www.umassmed.edu/punzolab/.)

Personal Story

My fascination with the eye began after attending an undergraduate lecture by Professor Walter Gehring at the University of Basel. His presentation on the evolution of the eye and the induction of extra eyes on limbs and antennas inspired me to join his laboratory for my undergraduate and graduate theses. After learning about eye development and evolution in the fruit fly, I decided to focus my fascination for the eye towards the goal of helping people affected by eye diseases, in particular retinal degenerative diseases. To that end I joined Dr. Cepko’s laboratory at Harvard Medical School for my postdoctoral training. I chose her laboratory because I wanted to obtain a strong foundation in vertebrate eye development, while working on a retinal degenerative disease. I always believed that to understand why nature sometimes fails, it is best to first understand how nature put something together, meaning how an organ develops and evolves, and then explore how it went down a particular path. After finishing my postdoctoral training with Dr. Cepko I decided to continue working on retinal degenerative diseases by leading my own research group at the University of Massachusetts Medical School. I strongly believe that treatment options for many blinding conditions will be within reach in the coming two decades, and I hope that this most precious of our senses, seeing, can one day be preserved for all.

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