Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration
Zhongjie Fu,
Chenxi Qiu,
Gael Cagnone,
Yohei Tomita,
Shuo Huang,
Bertan Cakir,
Yumi Kotoda,
William Allen,
Edward Bull,
James D. Akula,
Jean-Sébastien Joyal,
Ann Hellström,
Saswata Talukdar,
Lois E.H. Smith
Affiliations
Zhongjie Fu
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; The Manton Center for Orphan Disease, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Chenxi Qiu
Department of Medicine, Division of Translational Therapeutics, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Gael Cagnone
Department of Pediatrics, Pharmacology and Ophthalmology, CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Qc H3A 0C4, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, Qc H3A 0C4, Canada
Yohei Tomita
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Shuo Huang
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Bertan Cakir
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Yumi Kotoda
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
William Allen
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Edward Bull
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
James D. Akula
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Jean-Sébastien Joyal
Department of Pediatrics, Pharmacology and Ophthalmology, CHU Sainte-Justine Research Center, Université de Montréal, Montreal, Qc H3A 0C4, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, Qc H3A 0C4, Canada
Ann Hellström
Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Göteborg 405 30, Sweden
Saswata Talukdar
Cardiometabolic Diseases, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA
Lois E.H. Smith
Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Summary: 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.
