Abstract
Maleic acid was formulated in 0.7% saline and injected intravitreally in rabbits in order to evaluate ocular safety and tolerability. Maleic acid was formulated within a narrow pH range (2-3), administered in a fixed volume (100 µl), and concentrations ranged from 0.00 to 2.00 mg/eye (0.00 to 12.30 mM vitreous). Ocular evaluations were conducted at 2, 4, and 8 days post injection. Ocular irritation responses were observed at doses from 0.50 mg/eye (3.07 mM vitreous) to 2.00 mg/eye (12.30 mM vitreous) and included conjunctival redness and scleral swelling. Chemosis was observed at 2.00 mg/eye (12.30 mM vitreous). Funduscopic evaluations revealed enlarged retinal blood vessels and optic disk swelling at doses ≥1.50 mg/eye (9.22 mM vitreous), retinal folds and retinal discoloration at 2.00 mg/eye (12.30 mM vitreous). Histopathologic evaluations on days 4 and 8 post injection revealed retinal degeneration at doses ≥1.0 mg/eye (6.15 mM vitreous), conjunctival inflammation at doses ≥1.5 mg/eye (9.22 mM vitreous), and retinal pigment epithelial hypertrophy, optic nerve demyelination, anterior chamber fluid, and conjunctival fibrosis at 2.00 mg/eye (12.30 mM vitreous) maleic acid. The data suggest that maleic acid formulations at ≥1.00...Continue Reading
References
Dec 4, 1987·Neuroscience Letters·H Wolburg, K Berg
Jun 23, 1995·Neuroscience Letters·D V Pow, D K Crook
Jul 1, 1993·Journal of Chemical Neuroanatomy·A ReichenbachL Hertz
Aug 1, 1996·Trends in Neurosciences·E Newman, A Reichenbach
May 1, 1997·Experimental Eye Research·R C RoseS P Richer
Apr 1, 1998·Proceedings of the Society for Experimental Biology and Medicine·R C RoseA M Bode
Mar 25, 2000·Neurochemistry International·D HusterW Reichelt
May 12, 2004·Nature Reviews. Drug Discovery·Napoleone FerraraWilliam Novotny
Jun 1, 2005·Vision Research·Mike FranckeAndreas Bringmann
Apr 1, 1938·The Biochemical Journal·E J Morgan, E Friedmann
May 1, 1938·The Biochemical Journal·E J Morgan, E Friedmann
Jul 29, 2008·Investigative Ophthalmology & Visual Science·Barry S Winkler
Feb 10, 2009·Current Diabetes Reviews·Marta S FigueroaSusana Noval
Feb 12, 2011·AAPS PharmSciTech·Michelle T MarraKatsuhiko Sueda
Mar 1, 2010·Expert Review of Clinical Pharmacology·Stuart J McGimpsey, Usha Chakravarthy
Citations
Oct 21, 2015·Toxicology and Applied Pharmacology·Wenhu HuangAida Sacaan
Mar 22, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mei-Ling HouTung-Hu Tsai
Jul 11, 2018·Pharmaceutical Research·Shirley A AguirreWenhu Huang