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How Inflammation Triggers Photoreceptor Regeneration
The degeneration and death of photoreceptor cells is a primary cause of blinding diseases like age-related macular degeneration and retinitis pigmentosa.
A fundamental focus in the study of these degenerative retinal diseases, as well as neurodegenerative diseases like Alzheimers, is the role inflammation plays in fueling retinal cell and neuron degeneration, and what can be done about it.
Basic science researchers investigating inflammation and cell death in the brain and retina often study zebrafish models. Unlike humans, when these creatures’ brain and retinal cells die, they have the ability to make new ones.
“These tiny fish naturally accomplish exactly what we would hope to achieve in patients with degenerative eye and brain diseases,” explains Peter Hitchcock, Ph.D., Professor of Ophthalmology and Cell and Developmental Biology. “We can learn a lot from them.”
New insights from their studies of zebrafish retinas have led Dr. Hitchcock and his colleague, Assistant Research Scientist Mikiko Nagashima, Ph.D., to view inflammation in a whole new way.
From their research, Drs. Hitchcock and Nagashima have established that when photoreceptors in the retinas of zebrafish are dying, they trigger an inflammatory response, and that this inflammation is required to make new photoreceptors. The inflammatory molecules signal specific cell types to begin to form new, regenerated photoreceptors.
“In zebrafish retinas, inflammation is a required step for photoreceptor regeneration,” explains Dr. Hitchcock. “This is in distinct contrast to inflammation in the human retina, where it is a part of healing, but can lead to degeneration and disease.”
Their game-changing finding will be pursued with a new NIH R21 grant, with Dr. Hitchcock as Principal Investigator and Dr. Nagashima as Co-Investigator. The R21 provides short-term funding to pursue ideas that break new ground.
“The subretinal space is where photoreceptors live and die in humans, and where they live, die and regenerate in zebrafish,” explains Dr. Hitchcock. “Our project explores the unique inflammatory environment of that space in zebrafish, and the specific cells within it that aid photoreceptor regeneration.
“The insights we gain may someday be used to combat degenerative eye diseases by inducing regrowth of photoreceptor or other cells in the human retina.”
Header image caption: Dr. Nagashima injects CRISPR-Cas9 components into single cell stage zebrafish embryos
