Protective effects of sumatriptan against optic nerve injury in rats via modulation of kynurenine pathway, oxidative stress and apoptosis

Moein Ala; Razieh Mohammad Jafari; Leila Aghajanpour; Mehdi Sanatkar; Masoud Aghsaei Fard; Sepideh Goudarzi; Amir Shadboorestan; Ahmad Reza Dehpour

Protective effects of sumatriptan against optic nerve injury in rats via modulation of kynurenine pathway, oxidative stress and apoptosis

2024

Introduction: Traumatic optic neuropathy (TON) is an acute visual dysfunction subsequent to head and neck trauma. Despite immense efforts, there is no effective treatment to minimize the damage caused by TON. Due to its anti-inflammatory and neuroprotective properties, we aimed to measure the effect of sumatriptan on optic nerve injury in rats. Methods: Bulldog forceps were used to induce optic nerve crush. Immediately after trauma, a single dose of sumatriptan was intravitreally injected and rats were just observed for 1 week. Visual evoked potential (VEP) was recorded to assess optic nerve function on days 2, 5, and 7 after optic nerve injury. Retinas were extracted seven days after trauma to assess molecular and microscopic changes. Results: Crushing force reduced cell survival, decreased the amplitude of the waves, and prolonged their latency in VEP. In contrast, sumatriptan significantly increased cell survival and shortened the latency of P2 and N2 waves. Likewise, sumatriptan significantly decreased the tissue levels of toll-like receptor 4 (TLR4), phosphorylated extracellular signal-regulated kinase (p-ERK), malondialdehyde (MDA), indole-amine 2,3-dioxygenase 1 (IDO), tumor necrosis factor α (TNF-α), interferon γ (INF-γ), and kynurenine in the retinas of rats. Conclusion: These findings suggest that sumatriptan can enhance retinal cell viability, improve optic nerve function, and decrease inflammation, possibly through attenuation of TLR4, ERK, and kynurenine signaling pathways. Thus, future clinical trials should assess the efficacy of low-dose intravitreal sumatriptan for patients with TON.

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