Ocular Safety of Intravitreal Propranolol in a Rabbit Model

Abstract

Purpose: Propranolol, as a nonselective β-adrenergic receptor blocker, may be a new promising treatment for various ocular vasculopathies. To determine whether propranolol may be used safely as an intraocular drug, the ocular safety of intravitreal propranolol in rabbits was studied by ophthalmoscopy, electrophysiological testing, and histopathologic analysis.

Methods: Twenty eight New Zealand Albino rabbits were categorized into 4 groups (n=7). Each animal was randomized to receive either 15µL BSS alone or propranolol at 15µg, 30µg, and 60µg/15µL in the right eye by intravitreal injection. Ophthalmoscopy and electroretinogram (ERG) recordings were made before and 1 and 4 weeks after injection. Eventually, the rabbits were euthanized and the retinas were examined for histopathologic evaluations and immunohistochemical study for glial fibrillary acidic protein (GFAP).

Results: Fundus examinations were unremarkable in all eyes. ERG evidenced no significant difference between control and propranolol-injected eyes at doses of 15µg and 30µg/15µL. However, mean scotopic b-wave amplitude measured 4 weeks after injection was significantly reduced in eyes receiving 60µg/15µL propranolol (p=0.06). Light microscopy of retina was unremarkable in all eyes. GFAP immune-reactivity of retinal Muller cells supported the ERG results; it was significantly increased in the 60µg/µL-injected eyes but was not different between control and propranolol-injected eyes at doses of 15µg and 30µg/15µL.

Conclusions: Our study did not find evidence of retinal toxicity from intravitreal injection of less than 30µg/15µL propranolol in rabbits.

Keywords: 561 injection • 688 retina