Acute Loss of TrkB Signaling Impairs the Survival of Mature Retinal Ganglion Cells and Retinal Function
4 affiliations
- 1Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
- 2Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
- 3Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan
- 4Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan
Abstract
Purpose: To determine whether acute loss of tropomyosin receptor kinase B (TrkB) signaling in mature retinal ganglion cells (RGCs) induces RGC degeneration and retinal functional impairment in the adult mouse retina.
Methods: TrkB deletion was induced in adult TrkBflox/flox mice by intravitreal administration of adeno-associated virus serotype 2 (AAV2)-Cre. AAV2-Cre tropism was examined using tdTomato reporter mice and retinal cell markers. TrkB, RNA-binding protein with multiple splicing (RBPMS), calretinin, glutamine synthetase, and recoverin protein levels were assessed by western blotting. RGC survival was evaluated by RBPMS immunostaining of retinal flatmounts. Retinal function was assessed by analyzing the second-order kernel of multifocal electroretinography. Acute TrkB deletion was compared with developmental TrkB deletion in TrkBflox/flox;c-kit-Cre mice.
Results: AAV2-Cre predominantly transduced RBPMS-positive RGCs, with little overlap with calretinin-positive amacrine cells, glutamine synthetase–positive Müller glia, or recoverin-positive photoreceptors. AAV2-Cre administration at 7 weeks of age reduced TrkB protein levels. RBPMS protein levels and RBPMS-positive RGC density were significantly decreased 5 weeks after AAV2-Cre administration at 12 weeks of age, whereas calretinin, glutamine synthetase, and recoverin protein levels were unchanged. Retinal responses of the second-order kernel were also significantly reduced. In contrast, RGC density was not significantly altered in TrkBflox/flox;c-kit-Cre mice at 12 weeks of age.
Conclusions: Acute TrkB deletion in the adult retina induces RGC degeneration and impairs retinal function, whereas no significant reduction in RGC density was detected following developmental TrkB deletion at 12 weeks of age. These findings indicate that endogenous TrkB signaling is required for mature RGC maintenance and suggest that reduced TrkB signaling may contribute to glaucomatous RGC degeneration.
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BibTeX
@article{kitamura2026acute,
title = {{Acute Loss of TrkB Signaling Impairs the Survival of Mature Retinal Ganglion Cells and Retinal Function}},
author = {Yuta Kitamura and Kazuhiko Namekata and Xiaoli Guo and Youichi Shinozaki and Sari Honda and Euido Nishijima and Takahiko Noro and Chikako Harada and Takayuki Harada},
journal = {Investigative Ophthalmology \& Visual Science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.75},
url = {https://doi.org/10.1167/iovs.67.12.75},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Acute Loss of TrkB Signaling Impairs the Survival of Mature Retinal Ganglion Cells and Retinal Function
AU - Yuta Kitamura
AU - Kazuhiko Namekata
AU - Xiaoli Guo
AU - Youichi Shinozaki
AU - Sari Honda
AU - Euido Nishijima
AU - Takahiko Noro
AU - Chikako Harada
AU - Takayuki Harada
PY - 2026
DA - 2026/10/28
JO - Investigative Ophthalmology & Visual Science
DO - 10.1167/iovs.67.12.75
UR - https://doi.org/10.1167/iovs.67.12.75
AB - Purpose: To determine whether acute loss of tropomyosin receptor kinase B (TrkB) signaling in mature retinal ganglion cells (RGCs) induces RGC degeneration and retinal functional impairment in the adult mouse retina. Methods: TrkB deletion was induced in adult TrkBflox/flox mice by intravitreal administration of adeno-associated virus serotype 2 (AAV2)-Cre. AAV2-Cre tropism was examined using tdTomato reporter mice and retinal cell markers. TrkB, RNA-binding protein with multiple splicing (RBPMS), calretinin, glutamine synthetase, and recoverin protein levels were assessed by western blotting. RGC survival was evaluated by RBPMS immunostaining of retinal flatmounts. Retinal function was assessed by analyzing the second-order kernel of multifocal electroretinography. Acute TrkB deletion was compared with developmental TrkB deletion in TrkBflox/flox;c-kit-Cre mice. Results: AAV2-Cre predominantly transduced RBPMS-positive RGCs, with little overlap with calretinin-positive amacrine cells, glutamine synthetase–positive Müller glia, or recoverin-positive photoreceptors. AAV2-Cre administration at 7 weeks of age reduced TrkB protein levels. RBPMS protein levels and RBPMS-positive RGC density were significantly decreased 5 weeks after AAV2-Cre administration at 12 weeks of age, whereas calretinin, glutamine synthetase, and recoverin protein levels were unchanged. Retinal responses of the second-order kernel were also significantly reduced. In contrast, RGC density was not significantly altered in TrkBflox/flox;c-kit-Cre mice at 12 weeks of age. Conclusions: Acute TrkB deletion in the adult retina induces RGC degeneration and impairs retinal function, whereas no significant reduction in RGC density was detected following developmental TrkB deletion at 12 weeks of age. These findings indicate that endogenous TrkB signaling is required for mature RGC maintenance and suggest that reduced TrkB signaling may contribute to glaucomatous RGC degeneration.
SN - 0146-0404
SN - 1552-5783
ER -