Abstract
Hyperuricemia (HUA) is experiencing a rising incidence globally and can lead to a multitude of systemic complications. HUA is associated with various nervous system diseases and ocular impairments, yet the intricate relationship between HUA and fundus neurological changes remains unclear. To investigate the effect of HUA on retinal ganglion cells (RGCs), the HUA mouse model was established by daily intraperitoneal injections of potassium oxonate and a high-purine diet for 4 weeks. Structural and functional assessments of the retina were conducted using optical coherence tomography and electroretinography. Histological and molecular analyses were performed to evaluate inflammatory and apoptotic responses. Primary retinal neurons (PRNs) were isolated to simulate RGCs in vitro, enabling a comprehensive assessment of uric acid (UA)-induced cellular alterations. The HUA model showed elevated serum UA and a moderate increase in IOP. Retinal imaging revealed deposits in the vitreous and retina, accompanied by inner retinal layer thinning and RGC loss. Functional assessment indicated a reduction in photopic negative response amplitudes. Molecular analysis showed upregulation of inflammatory and apoptotic markers in retinal tissues. In vitro, HUA exposure resulted in reduced cell viability and synaptic connectivity in PRNs, along with elevated inflammatory and apoptotic levels. Activation of the nuclear factor-kappa B (NF-κB) pathway was identified as one of the mechanisms. NF-κB inhibitor BAY 11-7082 was applied to confirm its rescue effect. These findings suggested that HUA might contribute to structural and functional impairment to retinal neuron injury through inflammatory and apoptotic mechanisms, underscoring the importance of retinal health monitoring in HUA patients.