Advancing Optic Nerve Injury Treatment
New research sheds light on potential treatment for optic nerve injuries. A recent study has identified neural progenitor cell (NPC) therapy as a promising avenue for restoring damaged retinal ganglion cells (RGCs) and promoting optic nerve regeneration. The researchers also uncovered key regulators of these processes, including Vps35 and Syntaxin12. These findings may have important implications for the development of new treatments for optic neuropathies in humans. Read on to learn more about this groundbreaking research.
Damage to the optic nerve can lead to the degeneration of axons, resulting in a gradual decline in retinal ganglion cells (RGCs) and irreversible vision loss. Various factors can cause optic neuropathy, including head trauma, ischemia, metabolic disorders, genetic mitochondrial diseases, autoimmune inflammation, and infiltrative conditions.
The Optic Nerve Crush Model & The Optic Nerve Compression (ONCo) Injury Model
The optic nerve crush (ONCr) model is commonly used to study neuronal death and survival mechanisms and assess potential therapies for optic neuropathy. This model involves deliberately crushing the optic nerve to induce RGC apoptosis and has been combined with pharmacological and molecular approaches to test therapeutic agents. Previous studies have demonstrated the effectiveness of cellular treatments in this model, which has also contributed to research on RGC regeneration.
Recent studies introduced the optic nerve compression (ONCo) injury model as a less hazardous alternative to ONCr. ONCo minimally disrupts the ophthalmic artery and its blood flow by using Carlson DSEK graft forceps instead of self-clamping. Investigations into optic nerve transection (ONT) and ONCo have revealed insights into the origin and migration of myeloid and microglial cells in the optic nerve and optic nerve head (ONH). ONT, involving scissors to sever the nerve while maintaining retinal blood flow, is more effective at inducing RGC axon loss and retinal degeneration than ONCo. ONCo leaves around 50% of axons intact, allowing some RGCs to survive. Additionally, there is a higher concentration of microglia and myeloid cell proliferation in the optic nerve with ONCo compared to ONT, suggesting that complete transection of the optic nerve may impede the migration of reactive myeloid cells to the retina.
Investigating Neuroprotection and Regeneration
In a recent study, researchers aimed to investigate the neuroprotective and regenerative potential of neural progenitor cell (NPC) therapy in optic nerve injuries using both ONCr and ONCo models. They sought to understand the underlying mechanisms involved, with a particular focus on the role of Vps35 and Syntaxin12.
To the best of our knowledge, no study to date has performed a comparative analysis of different
types of optic nerve injuries. Therefore, we examined the patterns of damage and recovery using two distinct models of optic nerve injury, both of which avoid full transection of the optic nerve.
Therefore, they employed a combination of in vitro and in vivo experiments. In vitro experiments utilized R28 cells and primary RGCs to assess the effects of NPC therapy on cell viability, apoptosis, and neurite outgrowth. In vivo experiments involved a rat model of optic nerve injury to examine the impact of NPC therapy on optic nerve regeneration and functional recovery. Various techniques such as immunohistochemistry, Western blotting, and proteomics analysis were used to explore the mechanisms of neuroprotection and regeneration.
The study yielded several important findings:
NPC therapy effectively restored damaged RGCs and promoted optic nerve regeneration in both ONCr and ONCo models.
NPCs exerted their neuroprotective and regenerative effects by elevating neuroprotection factors, controlling inflammation, and maintaining mitochondrial homeostasis through the Wnt/β-catenin signaling pathway.
Vps35 and Syntaxin12 were identified as key regulators of these processes. Vps35 appeared to preserve mitochondrial function in ONCo, while Syntaxin12 restrained inflammation via the Wnt/β-catenin signaling pathway in ONCr.
Vps35 appears to play a role in preserving mitochondrial function in optic nerve compression (ONCo), while Syntaxin12 appears to restrain inflammation via the Wnt/β-catenin signaling pathway in optic nerve crush (ONCr). The researchers found that neural progenitor cell (NPC) therapy can effectively restore damaged retinal ganglion cells (RGCs) and promote optic nerve regeneration by elevating neuroprotection factors, controlling inflammation, and maintaining mitochondrial homeostasis through the Wnt/β-catenin signaling pathway. These findings suggest that Vps35 and Syntaxin12 may be key regulators of these processes.
These findings hold promise for the treatment of various optic neuropathies, including those resulting from ischemic and crush injuries. However, further research is needed to assess the safety and efficacy of NPC therapy in human patients. This study represents a significant step towards developing innovative therapies for optic nerve injuries, offering hope for improved outcomes for individuals facing vision loss due to these conditions.