Related Experiment Video
Updated: Nov 17, 2025
10:02
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
32.7K
Carboxylesterase Activities and Protein Expression in Rabbit and Pig Ocular Tissues
Anam Hammid1, John K Fallon2, Toni Lassila3
1School of Pharmacy, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.
Molecular Pharmaceutics
|February 17, 2021
Summary
Ocular esterase activity and expression differ significantly between rabbit and pig eyes. This study provides crucial data for developing ophthalmic prodrugs and understanding drug metabolism in preclinical models.
Area of Science:
- Pharmacology and Toxicology
- Drug Metabolism
- Ocular Therapeutics
Background:
- Hydrolytic reactions are key in drug metabolism and prodrug activation, particularly for ophthalmic ester-containing drugs enhancing ocular permeation.
- Understanding ocular esterase activity and expression is vital for ophthalmic drug development, but data for preclinical species like rabbits and pigs are limited.
- Carboxylesterases (CESs) and arylacetamide deacetylase (AADAC) are critical enzymes involved in ester hydrolysis within ocular tissues.
Purpose of the Study:
- To systematically characterize the activity and protein expression of carboxylesterases (CESs) and arylacetamide deacetylase (AADAC) in ocular tissues of rabbits and pigs.
- To investigate species- and tissue-specific differences in ocular esterase profiles to inform ophthalmic drug design and preclinical studies.
Main Methods:
- Hydrolytic activities were assessed using generic (4-nitrophenyl acetate) and selective substrates for human CES1, CES2, and AADAC.
- Kinetics and inhibition studies were performed using established human enzyme inhibitors due to a lack of validated inhibitors for rabbit and pig CESs.
- Quantitative targeted proteomics was employed to measure protein expression levels of CESs and AADAC in seven ocular tissue homogenates.
Main Results:
- Rabbit ocular tissues exhibited variable CES1 and CES2 expression, with poor correlation between enzyme expression and hydrolytic activity.
- Pig ocular tissues predominantly expressed CES1, with low or absent levels of CES3 and AADAC.
- Significant species and tissue variations in ocular hydrolytic enzymes were identified between rabbits and pigs.
Conclusions:
- The distinct species and tissue-specific profiles of ocular esterases in rabbits and pigs must be considered in the design of esterase-dependent ophthalmic prodrugs.
- Findings are crucial for evaluating ocular effects of systemic drugs and for improving translational and toxicity studies in preclinical models.
- This research provides essential data to bridge the knowledge gap regarding ocular esterase characterization in commonly used preclinical species.
