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INTRODUCTION
INTRODUCTION
The vertebrate retina represents an experimentally accessible portion of the central nervous system and is an important model for understanding neuronal structure, function, and neurodegenerative processes more generally. This tissue has outstanding clinical and economic significance, as it provides the biological basis for vision - that sense most critical for maintaining quality of life. Within the retina, rod and cone photoreceptor cells act as the "pixels" to collect the light needed to form images. Our lab is focused on understanding rod and cone photoreceptor structure and function in health and disease to improve visual health.
RODS AND CONE PHOTORECEPTORS RELY ON PRECISELY STACKED MEMBRANES TO DETECT LIGHT
RODS AND CONE PHOTORECEPTORS RELY ON PRECISELY STACKED MEMBRANES TO DETECT LIGHT
Rods and cones are specialized nerve cells that allow humans and other vertebrates sight. They are fragile, and must maintain a variety of essential relationships with other cells in the retina -- to sustain function and survival. Although excellent progress has been made in understanding how rods and cones respond to light, far less is known regarding how cell structure is established and maintained, and how altered structure affects cell function and viability. Our lab is focused on understanding retinal diseases that result from alterations in photoreceptor structure.
The light-sensitive portions of both rod and cone photoreceptors are call "outer segments". They somewhat resemble long sleeves of pita breads - think 500-1000 pita breads! Each day, 50-100 pita breads are lost and must be replaced - a process called outer segment renewal. Interruptions and/or lack of fidelity in this process lead to debilitating loss-of-sight conditions, like retinitis pigmentosa and macular dystrophies.
DISCOVERING THE MOLECULAR BASIS OF ROD AND CONE PHOTORECEPTOR MEMBRANE ARCHITECTURE
DISCOVERING THE MOLECULAR BASIS OF ROD AND CONE PHOTORECEPTOR MEMBRANE ARCHITECTURE
“What is the secret of life?’ I asked. ‘I forget,’ said Sandra.
‘Protein,’ the bartender declared. ‘They found something out about protein.‘ ‘
Yeah,’ said Sandra, ‘that’s it.”
― Kurt Vonnegut, Cat's Cradle
To the best of our understanding, the secret of life remains something of a mystery; however in recent years, we have discovered that proteins are indeed the secret to properly structured (and functional) rods and cones. In particular, prph2 (formerly peripherin-2/rds), a specialized membrane protein, is required to generate and maintain rod and cone photoreceptor outer segments - the "pixels" of the light-sensitive retina. Without prph2 there is no vision. Unfortunately, inherited defects in prph2 cause a wide spectrum of human retinal diseases, including retinitis pigmentosa and macular degenerations.
Until now, the precise function of prph2 has remained mysterious. Our recent progress reveals that this protein directly shapes membranes into tight bends - to give outer segment disks their characteristic pita bread shape. Our ongoing studies are characterizing prph2 structure and interactions with other proteins to identify potential therapeutic targets, with the aim of restoring damaged rod and cone outer segment structure in order to preserve vision.
Technical Approaches
Technical Approaches
Our laboratory employs a variety of strategies, using approaches that include: molecular biology and genetics, bioinformatics, cell culture, preparative and analytical protein biochemistry, biophysical characterizations, immunohistochemistry, electron microscopy, and generation and characterization of transgenic frogs and mice.
Funding
Funding
This work has been made possible by the generous support of the following granting agencies:
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