Investigating the Source and Impact of Elevated Intraocular Insulin Levels in High Myopia

To investigate the origin, intraocular distribution, and metabolism of insulin in the eye and elucidate its relationship with high myopia.

Insulin localization in rat retinas was determined through immunofluorescence. Primary Müller cells from rat and human retinas were characterized to assess insulin expression. FITC-labeled insulin was administered via tail vein and intravitreal injections to evaluate transport dynamics. Vitreous samples from patients with varying macular pathologies were analyzed for insulin, C-peptide, and glucose levels, comparing high myopia patients with controls. Form-deprived guinea pigs underwent insulin and glucose quantification with insulin intervention experiments.

In patients with macular hole, high myopia patients showed significantly higher vitreous insulin (1.5-fold, p < 0.01) and C-peptide (1.8-fold, p < 0.001), with lower glucose (19%, p < 0.01) versus controls. Human vitreous insulin also correlated positively with macular pathology severity (p < 0.001). Insulin expression colocalized with Müller cell markers; Ins1/Ins2 mRNA was upregulated by serum deprivation. FITC tracing in SD rat showed that systemic insulin failed to penetrate the blood-retinal barrier, while intravitreal insulin primarily accumulated at the inner limiting membrane. Form-deprived guinea pigs mirrored this metabolic signature (higher insulin, lower glucose). Critically, exogenous insulin administration did not affect myopia progression (p > 0.05).

Müller cells produce insulin locally, creating a distinct intraocular environment. High myopia is associated with elevated insulin production with enhanced glucose utilization, but exogenous insulin did not significantly accelerate axial elongation, suggesting it is insufficient to further exacerbate myopia progression in this model.