Exploring the effects and mechanisms of the Qingmang No. 1 Formula in the treatment of traumatic optic neuropathy based on transcriptomics

To explore the effects and mechanisms of the Qingmang No. 1 Formula (QM-1F) in a rat model of traumatic optic neuropathy.

Thirty specific-pathogen-free (SPF) healthy male Wistar rats were divided into a sham operation group, a model group, and a QM-1F group using a random number table method, with 10 rats in each group. The rat model of traumatic optic neuropathy was established using the lateral optic nerve traction method. After modeling, rats in the QM-1F group received the QM-1F (13 g/kg) by gavage, whereas the sham operation and the model groups received equal volumes of distilled water intragastrically once a day for 14 consecutive days. Fundus color photography was used to observe the appearance of the optic disk and retina. A visual electrophysiology system was applied to detect flash visual evoked potentials (F-VEP). Optical coherence tomography was used to evaluate retinal morphology. Hematoxylin-eosin (HE) staining was performed to observe retinal histopathology. Transcriptomics technology was utilized to analyze differentially expressed genes (DEGs) in the rat retina, followed by functional annotation using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. An enzyme-linked immunosorbent assay was conducted to measure the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the retina. Western blotting was used to detect the protein expressions of fibronectin (FN), proteolipid protein 1 (PLP1), and myelin oligodendrocyte glycoprotein (MOG).

Compared with the sham operation group, the model group showed a pale optic disk, narrowed retinal blood vessels, and a thinned retina; the amplitude of N1-P1 in F-VEP was increased; and the number of cells in the layer of ganglion cells (GCL) decreased (P<0.05). Compared with the model group, the QM-1F group exhibited improved retinal morphology, decreased N1-P1 amplitude, ameliorated retinal histopathological structure, and increased number of GCL cells (P<0.05). Compared with the sham operation group, 1,296 DEGs (615 upregulated and 681 downregulated) were identified in the model group. GO functional enrichment analysis showed that DEGs were enriched in the membrane-related cellular components and transport functions. KEGG pathway enrichment analysis revealed the main enrichment in protein synthesis and energy metabolism, structure/adhesion, and nerve conduction-related pathways. Compared with the model group, 499 DEGs (368 upregulated and 131 downregulated) were identified in the QM-1F group. GO functional enrichment analysis indicated that DEGs were enriched in extracellular matrix, collagen, nerve coduction structures, and myelin-related functions. KEGG pathway enrichment analysis showed main enrichment in membrane-extracellular matrix interaction and survival signaling-related pathways as well as immune clearance and metabolic reprogramming-related pathways. The key DEGs included MOG and PLP1. Compared with the sham operation group, the SOD activity and the protein expressions of PLP1 and MOG in the retina of the model group decreased, whereas the MDA content and the expression of the FN protein increased (P<0.05). Compared with the model group, the expression of PLP1 protein increased and the expression of the FN protein decreased in the QM-1F group (P<0.05).

QM-1F alleviates retinal structural damage and promotes the recovery of visual pathway conduction function in the rat model of traumatic optic neuropathy. The potential mechanism of traumatic optic neuropathy may involve myelin repair, remodeling of the ECM, and regulation of oxidative stress.