Assessment of the safety of intravitreal injection of metoprolol tartrate in rabbits.

PURPOSE: To verify the safety of different doses of intravitreal metoprolol tartrate (MT) after intravitreal injection in rabbit eyes. METHODS: Animals were randomly assigned into 2 groups: group I received 50 µg of MT and group II 100 µg of MT. A volume of 0.05 mL of the drug solution was administered through an intravitreal injection, while the control eyes received an equal volume of saline solution. Safety was assessed by clinical observation, electroretinography (ERG) and histological evaluation. RESULTS: No evidence of clinical toxicity was observed. ERG waveforms from the MT treated eyes were similar to those recorded from the control eyes in dark-adapted state, amplitude and the implicit time are similar between the groups in light-adapted state, and their retinas had no signs of toxicity by histological evaluation 7 days after intravitreal injection. CONCLUSIONS: The intravitreal use of metoprolol at 50 and 100 µg dosages does not cause short-term retinal toxicity in rabbits.

PnPP-19 Peptide as a Novel Drug Candidate for Topical Glaucoma Therapy Through Nitric Oxide Release.

Purpose: Evaluation of PnPP-19 safety and efficacy in reducing the intraocular pressure (IOP) of animals with healthy (normotensive) and ocular hypertensive eyes. PnPP-19 is a synthetic peptide designed from Phoneutria nigriventer spider toxin PnTx2-6. Methods: Toxicity tests used chicken chorioallantoic membranes. Electroretinograms (ERGs) were recorded before and after administration of different doses of PnPP-19 on the eyes of Wistar rats. Histological sections of corneas and retinas were prepared. The efficacy of PnPP-19 in reducing IOP was evaluated for normotensive and ocular hypertensive animals using a tonometer. Ocular hypertension was induced in the right eye through injection of hyaluronic acid (HA) into the anterior chamber. ERG was recorded before and after glaucoma induction. The eyes were enucleated, and the corneas and retinas were histologically evaluated. Results: PnPP-19 showed no toxicity, being safe for ocular application. A single topical instillation of one eye drop of the peptide solution was able to reduce IOP, both in healthy and ocular hypertensive rats, for 24 hours, without eliciting any apparent toxicity. PnPP-19 is a nitric oxide inducer and the results suggest that it may improve the conventional outflow of aqueous humor (AH), preventing the progression of optic nerve degeneration. Conclusions: PnPP-19 has great potential to emerge as a promising drug for the treatment of ocular hypertension. Translational Relevance: We regard our findings as exciting progress in translational glaucoma research, combining drug discovery, natural product research, and pharmacology, which may contribute to the establishment of new therapies for the treatment of this disease.