RT Journal Article
SR Electronic
T1 SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900618
DO 10.26508/lsa.201900618
VO 3
IS 5
A1 Ema Ozaki
A1 Luke Gibbons
A1 Nuno GB Neto
A1 Paul Kenna
A1 Michael Carty
A1 Marian Humphries
A1 Pete Humphries
A1 Matthew Campbell
A1 Michael Monaghan
A1 Andrew Bowie
A1 Sarah L Doyle
YR 2020
UL https://www.life-science-alliance.org/content/3/5/e201900618.abstract
AB 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.