TY - JOUR
T1 - Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration
AU - Fu, Zhongjie
AU - Qiu, Chenxi
AU - Cagnone, Gael
AU - Tomita, Yohei
AU - Huang, Shuo
AU - Cakir, Bertan
AU - Kotoda, Yumi
AU - Allen, William
AU - Bull, Edward
AU - Akula, James D.
AU - Joyal, Jean Sébastien
AU - Hellström, Ann
AU - Talukdar, Saswata
AU - Smith, Lois E.H.
N1 - Funding Information:
L.E.H.S. is supported by NIH R24EY024868 , R01EY017017 , R01EY01717-13S1 , R01EY030904 , BCH IDDRC ( 1U54HD090255 ), Mass Lions Eye Foundation 75007; A.H. is supported by the Swedish Research Council (DNR# # 2020-01092 ), government grants under the ALF agreement ALFGBG-717971 , and the Wallenberg Clinical Scholars; Z.F. is supported by Boston Children's Hospital Manton Center for Orphan Disease Research 96307 , OFD/BTREC/CTREC Faculty Career Development Grant 97906, and Ophthalmology Foundation 85010, Little Giraffe Foundation 75449, and Mass Lions Eye Foundation 87820; J.D.A. is supported by R01EY028953 ; C.Q. is supported by Alzheimer's Association Research Fellowship AARF-19-617868; Y.T. is supported by the Manpei Suzuki Diabetes Foundation , Alcon Research Institute 77486 , and Bert M. Glaser, MD Award 80131 .
Funding Information:
L.E.H.S. is supported by NIH R24EY024868, R01EY017017, R01EY01717-13S1, R01EY030904, BCH IDDRC (1U54HD090255), Mass Lions Eye Foundation 75007; A.H. is supported by the Swedish Research Council (DNR# #2020-01092), government grants under the ALF agreement ALFGBG-717971, and the Wallenberg Clinical Scholars; Z.F. is supported by Boston Children's Hospital Manton Center for Orphan Disease Research 96307, OFD/BTREC/CTREC Faculty Career Development Grant 97906, and Ophthalmology Foundation 85010, Little Giraffe Foundation 75449, and Mass Lions Eye Foundation 87820; J.D.A. is supported by R01EY028953; C.Q. is supported by Alzheimer's Association Research Fellowship AARF-19-617868; Y.T. is supported by the Manpei Suzuki Diabetes Foundation, Alcon Research Institute 77486, and Bert M. Glaser, MD Award 80131. Concept and design, L.E.H.S, Z.F. and S.T.; formal analysis, Z.F. C.Q. G.C. S.T. and L.E.H.S.; investigation, Z.F.; writing-original draft, Z.F. C.Q. and G.C.; writing-review & editing, L.E.H.S. A.H. and S.T.; resources, S.T.; funding acquisition, L.E.H.S.; methodology, Z.F. C.Q. G.C. Y.T. S.H. B.C. Y.K. W.A. E.B. JS.J. and J.D.A.; supervision, L.E.H.S, S.T. and A.H. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. S.T. is an employee of Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Kenilworth, NJ, USA, and a stockholder in Merck & Co. Kenilworth, NJ, USA.
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/4/23
Y1 - 2021/4/23
N2 - The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Müller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4–10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Müller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Müller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Müller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.
AB - The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Müller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuroprotectant, from postnatal week 4–10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Müller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Müller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Müller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.
KW - Cellular Neuroscience
KW - Neuroscience
KW - Sensory Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85104138775&partnerID=8YFLogxK
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U2 - 10.1016/j.isci.2021.102376
DO - 10.1016/j.isci.2021.102376
M3 - Article
AN - SCOPUS:85104138775
SN - 2589-0042
VL - 24
JO - iScience
JF - iScience
IS - 4
M1 - 102376
ER -