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SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration

Authors: Ema Ozaki; Luke Gibbons; Nuno GB Neto; Paul Kenna; Michael Carty; Marian Humphries; Pete Humphries; +4 Authors

SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration

Abstract

Retinal degeneration is the leading cause of incurable blindness worldwide and is characterised by progressive loss of light-sensing photoreceptors in the neural retina. SARM1 is known for its role in axonal degeneration, but a role for SARM1 in photoreceptor cell degeneration has not been reported. SARM1 is known to mediate neuronal cell degeneration through depletion of essential metabolite NAD and induction of energy crisis. Here, we demonstrate that SARM1 is expressed in photoreceptors, and using retinal tissue explant, we confirm that activation of SARM1 causes destruction of NAD pools in the photoreceptor layer. Through generation of rho−/−sarm1−/− double knockout mice, we demonstrate that genetic deletion of SARM1 promotes both rod and cone photoreceptor cell survival in the rhodopsin knockout (rho−/−) mouse model of photoreceptor degeneration. Finally, we demonstrate that SARM1 deficiency preserves cone visual function in the surviving photoreceptors when assayed by electroretinography. Overall, our data indicate that endogenous SARM1 has the capacity to consume NAD in photoreceptor cells and identifies a previously unappreciated role for SARM1-dependent cell death in photoreceptor cell degeneration.

Country
Ireland
Keywords

Male, 570, Rhodopsin, 610, Retina, Mice, Retinal Rod Photoreceptor Cells, Electroretinography, Animals, Photoreceptor Cells, Retinal degeneration, photoreceptor cell degeneration, Research Articles, Vision, Ocular, Armadillo Domain Proteins, Mice, Knockout, Retinal Degeneration, NAD, incurable blindness, Mice, Inbred C57BL, Cytoskeletal Proteins, Disease Models, Animal, Retinal Cone Photoreceptor Cells, Female, Retinitis Pigmentosa

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
45
Top 10%
Top 10%
Top 1%
Green
gold