Metabolic Threat to Vision: Hyperuricemia-Associated Retinal Ganglion Cell Damage Through Inflammatory and Apoptotic Pathways

Background 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 is not clear. Methods To investigate the effect of HUA to retinal ganglion cells (RGCs), HUA mouse model was established by daily intraperitoneal injections of potassium oxonate and a high-purine diet for 4 weeks. Intraocular pressure (IOP), and serum uric acid (UA) levels were measured. Retinal structure and function were assessed. Histological staining and molecular analyses were performed. Primary retinal neurons (PRNs) were isolated to simulate RGCs in vitro , enabling a comprehensive assessment of UA-induced cellular alterations. Results An increase in IOP and serum UA levels were found in the modeling mice. White deposits were observed in the vitreous and retina, along with thinning of the inner retinal layer and RGC loss. The modeling mice showed retinal functional impairment, presented as a decrease in photopic negative response (PhNR) amplitudes. Increased levels of inflammatory and apoptotic factors were detected in the retinas. In vitro , HUA led to decreased cell viability and synaptic connections, increased inflammatory and apoptotic levels of PRNs. Activation of the NF-κB pathway was identified as one of the mechanisms. NF-κB inhibitor BAY 11-7082 was applied to confirm its rescue effect. Conclusions These findings demonstrated that HUA induced structural and functional impairment to retinal neurons by promoting apoptosis and inflammation in the RGC layer, underscoring the importance of retinal health monitoring in HUA patients.