Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival.
Slc2a1
GLUT1
glucose depervation
photoreceptors
retina
rhodopsin
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
27
05
2022
received:
22
03
2022
accepted:
10
06
2022
entrez:
29
6
2022
pubmed:
30
6
2022
medline:
1
7
2022
Statut:
ppublish
Résumé
Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.
Identifiants
pubmed: 35766190
doi: 10.1096/fj.202200369R
pmc: PMC9438481
mid: NIHMS1816142
doi:
Substances chimiques
Glucose Transporter Type 1
0
SLC2A1 protein, human
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22428Subventions
Organisme : NEI NIH HHS
ID : P30 EY025585
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY026525
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY012042
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY031324
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY032462
Pays : United States
Organisme : NIAAA NIH HHS
ID : T32 AA007463
Pays : United States
Organisme : BLRD VA
ID : I01 BX005844
Pays : United States
Organisme : BLRD VA
ID : I01 BX002340
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY001583
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005233
Pays : United States
Informations de copyright
© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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