Stem cells ameliorate neurotrauma-induced visual disturbances and retinal degeneration via broad normalization of β-catenin-related signaling

TL;DR

Stem cells help reduce vision problems and retinal damage after brain injury by restoring a key signaling pathway.

Contribution

This study shows that MSC therapy improves TBI-induced retinal degeneration through β-catenin signaling normalization.

Findings

MSC treatment improved visual function and preserved retinal structure in TBI rats.

MSCs reduced neuronal apoptosis and restored β-catenin signaling in both in vivo and in vitro models.

MSCs mitigated mitochondrial dysfunction and ROS overproduction in injured retinal cells.

Abstract

Traumatic brain injury (TBI) is associated with visual dysfunction and retinal degeneration, but the underlying mechanisms and therapeutic options remain limited. Mesenchymal stem cells (MSCs) have shown neuroprotective effects in various central nervous system injuries, including optic neuropathies.

To investigate the protective effects and mechanisms of MSC therapy in TBI-induced retinal degeneration using in vivo and in vitro models.

Repeated mild TBI was induced in adult male Wistar rats by lateral fluid percussion. On day 3 post-injury, rats received intravenous MSCs (4 × 10⁶ cells/ml/kg) or saline. Visual and neurological functions were assessed using the visual cliff test and modified neurological severity score (mNSS). Thirty-five days after TBI, retinal tissues were collected for histological and immunofluorescence analysis. In vitro, R28 retinal precursor cells underwent stretch injury (SI) and were then cocultured with MSCs. Cell viability, apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS), and β-catenin signaling were evaluated.

TBI caused visual deficits, brain injury, retinal ganglion cell loss, thinning of the ganglion cell complex, increased neuronal apoptosis, and decreased β-catenin-positive neurons. In vitro, SI led to decreased cell viability, increased apoptosis and autophagy, mitochondrial dysfunction, ROS overproduction, and reduced β-catenin expression. MSC treatment ameliorated both in vivo and in vitro injuries, restoring visual function, preserving retinal structure, and normalizing β-catenin-related pathways.

MSC therapy mitigates TBI-induced visual dysfunction and retinal degeneration, in association with β-catenin-related neuroprotective signaling, and may represent a promising strategy for treating TBI-related visual and retinal injury.

Figures