Melatonin alleviates retinal damage and visual function impairment by suppressing ROS/TXNIP/NLRP3 signalling and inhibiting microglial activation in rats with optic nerve crush injury.

This study aimed to investigate the protective mechanism of melatonin on retinal structure and optic nerve function after optic nerve crush (ONC) in a rat model. SD rats aged 6-8 weeks were used to establish an ONC model. The rats were intraperitoneally administered with melatonin daily after ONC. Loss of retinal ganglion cells (RGCs)/axons was confirmed by haematoxylin & eosin staining, optical coherence tomography, and retina flat mounts. Visual evoked potentials were measured to evaluate optic nerve function. Protein expression was determined by Western blot and immunofluorescence assays, and RT-PCR was performed to assess mRNA transcription. ONC can cause an increase in ROS accumulation in the optic nerve, with elevated expression levels of Iba1, F4/80, thioredoxin-interacting protein (TXNIP), NOD like receptor protein 3 (NLRP3), and cleaved caspase 1, as well as elevated transcription levels of IL-1β/IL-18. ONC can also cause structural damage to the retina, including thinning of the retina, reduction of RGCs and axons, and functional impairment of the optic nerve, including decreased N2‒P2 amplitudes, and prolonged latencies of P2. However, the intraperitoneal injection of melatonin after ONC can reduce the accumulation of ROS in the optic nerve; decrease the expression levels of Iba1, F4/80, TXNIP, NLRP3, and cleaved caspase 1; and also decrease the transcription levels of IL-1β/IL-18. Melatonin treatment also alleviates retinal damage and visual function impairment caused by ONC. These findings suggest that melatonin alleviates retinal damage and visual function impairment after ONC by suppressing the ROS/TXNIP/NLRP3 signalling pathway.