Insulin protects against progression of experimental glaucoma (EG) in nonhuman primates (NHP)

Abstract

Purpose : Topical insulin promotes robust regeneration of retinal ganglion cell (RGC) dendritic structure and presynaptic connections after injury in mice. Here we tested the hypothesis that daily administration of insulin eyedrops protects RGCs in NHP EG.

Methods : Unilateral EG was induced in N=12 rhesus macaques (ages 5-17 y) by laser photocoagulation of the trabecular meshwork. At baseline and throughout the study, bilateral imaging was done biweekly by OCT (Spectralis OCT2) to measure thickness of the circumpapillary retinal nerve fiber layer (RNFLT), macular ganglion cell complex (GCCT) and optic nerve head minimum rim width (MRW); scanning laser polarimetry (GDxVCC) was used to measure RNFL retardance (RNFL-R). At onset of EG, NHPs were randomized to receive a daily 50 µL eyedrop in the EG eye of either insulin (5 IU Humulin-R 100 IU/mL) or saline for 16 weeks. RGC function was assessed by the electroretinogram photopic negative response (PhNR) amplitude. Statistical analysis was done by repeated measures ANOVA with Tukey post-hoc tests.

Results : There were no significant changes over time for any parameter in fellow control (FC) eyes. In EG eyes at randomization, there were no significant differences between insulin and saline groups for RNFLT, GCCT, MRW, or RNFL-R. However, at the final treatment time point, while all four structural parameters were significantly worse in the saline group (all P<0.0001), only GCCT had changed in the insulin-treated group (Figs 1,2). During the treatment period, the rate of EG progression was significantly faster in saline than insulin-treated eyes for all four structural parameters (all P<0.05). All four rates were significantly faster than zero in the saline eyes, but GCCT, MRW and RNFL-R rates were not different from zero in the insulin-treated eyes, implying protection. PhNR:b-wave ratio was not significantly different between saline and insulin-treated eyes at randomization but became worse only in the saline group at the final ERG time point (P=0.03). Intraocular pressure was not significantly different between insulin and saline groups during either EG pre-treatment or treatment periods. There were no adverse effects of topical insulin and no changes in fasting blood glucose or glycosylated hemoglobin.

Conclusions : Treatment with topical insulin substantially decreased progression of glaucomatous damage in this NHP model without altering IOP or blood glucose.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.