Neuroinflammation-Associated Optic Structural-Functional Degeneration in Early Diabetic Optic Neuropathy.

Abstract

BACKGROUND: Diabetic optic neuropathy (DON) is characterized by optic nerve degenerative changes, which may progress to optic atrophy and even blindness. Although DON is relatively common, its early diagnosis remains challenging. This study employed a noninvasive in vivo imaging combined histopathological assessment system to investigate changes in optic structural-functional degeneration in DON models. METHODS: Animals were divided into experimental group (8 db/db mice) and control group (8 db/m mice). Blood glucose, body weight, intraocular pressure, peripapillary retinal nerve fiber layer (RNFL), total retinal thickness (TRT), and visual behavior were at 2, 3, 4, 5 and 8 months old. Furthermore, histopathological and molecular validations were performed on the peripapillary retinal tissue. RESULTS: Across the 6-month follow-ups, db/db mice remained hyperglycemic and obese. Compared with the control group, db/db mice showed significant thinning of the peripapillary RNFL and TRT, and pyroptosis of retinal gangolion cells at 3 months old, suggesting optic nerve degeneration. Meanwhile, decreased visual acuity and increased contrast sensitivity thresholds confirmed the establishment of an early DON model. Thinning of the TRT at 8 months old was found to be linearly correlated with decreased visual acuity, but not with contrast thresholds in the DON group. No significant differences of intraocular pressure were found between groups at any time point. CONCLUSIONS: Db/db mice provide a reliable model for early DON study. Retinal structural impairment was closely associated with visual dysfunction, underscoring the link between neurodegeneration and functional loss. These findings may facilitate early diagnosis and treatment of DON.