PURPOSE: Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), is characterized by progressive loss of photoreceptor cells and retinal pigment epithelium (RPE) leading to vision loss. Drugs that protect photoreceptors and RPE may offer significant structural and functional benefits. Alpha-2 adrenergic receptor agonists have shown efficacy in multiple experimental models of retinal disease and slowed GA lesion growth in human clinical trials, suggesting they may be beneficial as novel GA therapeutics. Herein, we used a blue light retinal degeneration model to investigate the effects of a novel alpha-2 adrenergic receptor agonist, BL1106, on outer retinal structure and electrophysiological function.

METHODS: An alpha-2 adrenergic receptor agonist, BL1106, vehicle, or brimonidine was prophylactically administered to male Sprague–Dawley rats either via daily intraperitoneal (i.p.) injections starting 1 hour prior to blue light exposure or by subcutaneous (s.c.) osmotic mini-pumps starting 2 days prior to blue light exposure at 1 mg/kg/day. Treatments continued until day 7 or 14 post blue light exposure. Retinal thickness was measured by optical coherence tomography (OCT) on day 7 or 11. Electroretinography (ERG; scotopic and photopic a- and b-wave) function was evaluated on day 14 in the osmotic mini-pump cohort.

RESULTS: Mean retinal thickness was significantly greater in animals that received BL1106 or brimonidine daily i.p. injections compared to vehicle controls on day 11 post-exposure (p<0.0001), demonstrating a protective effect of alpha2-adrenergic agonist treatment. animals treated with bl1106 via osmotic mini-pump showed a significantly greater mean retinal thickness compared to those animals that received osmotic mini-pump delivery of vehicle p="0.0003)" or brimonidine p><0.0086) on day 7 post-exposure suggesting improved structural effects with bl1106 treatment. these findings corresponded with improved erg function in animals receiving bl1106 but not brimonidine on day 14 post-exposure compared to vehicle controls.>

CONCLUSIONS: A novel alpha-2 adrenergic agonist, BL1106, preserves retinal thickness and ERG function in a blue light model of retinal degeneration, suggesting its potential as a promising future therapeutic for AMD.