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Single-Cell Profiling of Zebrafish Retinal Ganglion Cells Reveal an Injury Response Mediated by Cell Dedifferentiation and Leukocytes [RNA-Seq]

ABSTRACT: Retinal ganglion cells (RGCs) are the sole projection neurons connecting the retina to the brain and therefore play a critical role in vision. Death of RGCs during glaucoma results in irreversible loss of vision as RGCs do not regenerate after injury in the human eye. There are no FDA approved drugs to prevent RGC death and/or promote RGC survival after injury. There is a critical need to better understand the molecular underpinnings of neuroprotection in vivo that can then be leveraged to develop new therapeutic approaches. Unlike mammals, zebrafish RGCs are resilient to injury and this study characterizes zebrafish retinal ganglion cell injury response to optic nerve transection (ONT) using isl2b:eGFP transgenic fish line, single cell and bulk RNA sequencing and in situ hybridization. We demonstrate that zebrafish RGCs do not show subtype specific resilience to injury but show a distinct temporal injury response which includes an increase in subtype 3, a cell population having progenitor and regenerative identity.

ORGANISM(S): Danio rerio

PROVIDER: GSE284728 | GEO | 2025/06/02

REPOSITORIES: GEO

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Single-Cell Profiling of Zebrafish Retinal Ganglion Cells Reveal an Injury Response Mediated by Cell Dedifferentiation and Leukocytes [scRNA-Seq]

Project description:Retinal ganglion cells (RGCs) are the sole projection neurons connecting the retina to the brain and therefore play a critical role in vision. Death of RGCs during glaucoma results in irreversible loss of vision as RGCs do not regenerate after injury in the human eye. There are no FDA approved drugs to prevent RGC death and/or promote RGC survival after injury. There is a critical need to better understand the molecular underpinnings of neuroprotection in vivo that can then be leveraged to develop new therapeutic approaches. Unlike mammals, zebrafish RGCs are resilient to injury and this study characterizes zebrafish retinal ganglion cell injury response to optic nerve transection (ONT) using isl2b:eGFP transgenic fish line, single cell and bulk RNA sequencing and in situ hybridization. We demonstrate that zebrafish RGCs do not show subtype specific resilience to injury but show a distinct temporal injury response which includes an increase in subtype 3, a cell population having progenitor and regenerative identity.

2025-06-02 | GSE284729 | GEO

Intercellular communication atlas reveals Oprm1 as a neuroprotective factor for retinal ganglion cells

Project description:The neuronal cell death results in neurodegenerative diseases. The extracellular environment plays a critical role in regulating cell viability. In this study, we explore how intercellular communication contributes to the survival of retinal ganglion cells (RGCs) following the optic nerve crush (ONC). By performing single-cell RNA-seq on whole retinal cells, we observed transcriptomic responses in non-RGC retinal cells to the injury, with astrocytes and Müller glia having the most interactions with RGCs. By comparing the RGC subclasses showing distinct resilience cell death, we identified top 47 interactions that are stronger in the high-survival RGCs, likely representing neuroprotective interactions. We performed functional assays on one of the receptors, Mu-opioid receptor (Oprm1). Although Oprm1 is preferentially expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), its neuroprotective effect could be transferred to multiple RGC subclasses by specific overexpressing Oprm1 in pan-RGCs. Our study provides an atlas of cell-cell interactions in both intact and post-ONC retina and an effective strategy to predict molecular mechanisms in neuroprotection, underlying the principal role played by extracellular environment in supporting neuron survival.

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Transcription profiling of mouse optic nerves as a model for axonal injury

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Retinal ganglion cell survival after severe optic nerve injury is modulated by crosstalk between JAK/STAT signaling and innate immune responses in the zebrafish retina

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