Adiponectin receptor 1 conserves docosahexaenoic acid and promotes photoreceptor cell survival.
The identification of pathways necessary for photoreceptor and retinal pigment epithelium (RPE) function is critical to uncover therapies for blindness. Here we report the discovery of adiponectin receptor 1 (AdipoR1) as a regulator of these cells' functions. Docosahexaenoic acid (DHA) is avidly retained in photoreceptors, while mechanisms controlling DHA uptake and retention are unknown. Thus, we demonstrate that AdipoR1 ablation results in DHA reduction. In situ hybridization reveals photoreceptor and RPE cell AdipoR1 expression, blunted in AdipoR1(-/-) mice. We also find decreased photoreceptor-specific phosphatidylcholine containing very long-chain polyunsaturated fatty acids and severely attenuated electroretinograms. These changes precede progressive photoreceptor degeneration in AdipoR1(-/-) mice. RPE-rich eyecup cultures from AdipoR1(-/-) reveal impaired DHA uptake. AdipoR1 overexpression in RPE cells enhances DHA uptake, whereas AdipoR1 silencing has the opposite effect. These results establish AdipoR1 as a regulatory switch of DHA uptake, retention, conservation and elongation in photoreceptors and RPE, thus preserving photoreceptor cell integrity.
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
Dennis S
DS
Rice
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Jorgelina M
JM
Calandria
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
William C
WC
Gordon
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Bokkyoo
B
Jun
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Yongdong
Y
Zhou
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
Claire M
CM
Gelfman
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Songhua
S
Li
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Minghao
M
Jin
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Eric J
EJ
Knott
The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
Bo
B
Chang
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
Alex
A
Abuin
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
Tawfik
T
Issa
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
David
D
Potter
Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, Texas 77381, USA.
Kenneth A
KA
Platt
Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans, Louisiana 70112, USA.
Nicolas G
NG
Bazan
D000818:Animals; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004596:Electroretinography; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000502:physiology*; D054419:Receptors, Adiponectin / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000502:physiology*
D010713:Phosphatidylcholines; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; D004281:Docosahexaenoic Acids