Evidence map›Paper›PMID 40896888›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2025

Characterization of hydrolase activity in ocular tissues of humans and preclinical species.

Mengyue Li, Donglu Zhang, Robert S Jones, Lionel Cheruzel, S Cyrus Khojasteh, Hsu-Hsin Chen, Emel Adaligil, Treefa Shwani, Leah A Owen, Ivana K Kim and 2 more

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In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Mengyue LiDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California; Department of Pharmaceutical Chemistry, School of Pharmacy, University of Kansas, Lawrence, Kansas.
Donglu ZhangDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California.
Robert S JonesDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California.
Lionel CheruzelDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California.
S Cyrus KhojastehDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California.
Hsu-Hsin ChenDepartment of Human Pathobiology & OMNI Reverse Translation, Genentech, Inc, South San Francisco, California.
Emel AdaligilDepartment of Peptide Therapeutics, Genentech, Inc, South San Francisco, California.
Treefa ShwaniDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Neuroscience Graduate Program, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York.
Leah A OwenDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, The University of Utah, Salt Lake City, Utah; Department of Population Health Sciences, University of Utah School of Medicine, The University of Utah, Salt Lake City, Utah; Division of Ophthalmology, Department of Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Obstetrics and Gynecology, University of Utah School of Medicine, The University of Utah, Salt Lake City, Utah.
Ivana K KimDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Retina Service, Massachusetts Eye & Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
Margaret M DeAngelisDepartment of Ophthalmology, Ross Eye Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Neuroscience Graduate Program, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Department of Ophthalmology and Visual Sciences, University of Utah School of Medicine, The University of Utah, Salt Lake City, Utah; Department of Population Health Sciences, University of Utah School of Medicine, The University of Utah, Salt Lake City, Utah; Genetics, Genomics and Bioinformatics Graduate Program, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York; Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York/University at Buffalo, Buffalo, New York.
Bin MaDepartment of Drug Metabolism and Pharmacokinetics, Genentech, Inc, South San Francisco, California. Electronic address: ma.bin@gene.com.

Funding

NEI NIH HHS K08 EY031800NEI NIH HHS R01 EY031209
6 · The paper itself

Abstract

Hydrolases in the eye play an important role in the metabolism of ophthalmic drugs, especially those administered locally to the eyes. With the growing interest in peptide-based therapeutics for treating eye disease, it has become increasingly important to characterize the enzymatic activities of ocular tissues against both small molecules and peptides to better understand their ocular metabolism. In this study, we characterized the activities of hydrolases, including carboxylesterase 1 and 2, arylacetamide deacetylase, paraoxonases, cytidine deaminase, fatty-acid amide hydrolase, and peptidases by incubating probe substrates in whole eye homogenates and vitreous humors from human donors and 3 preclinical species, including New Zealand White rabbits, Gottingen minipigs, and Cynomolgus monkeys. The enzyme activities were also tested in human liver S9 fractions as a comparison. The activities of all the investigated enzymes were detected and characterized in eye homogenates of humans and the 3 preclinical species, except that arylacetamide deacetylase activity was only observed in rabbits. To our knowledge, the activities of paraoxonases, cytidine deaminase, and fatty-acid amide hydrolase were identified for the first time in the eyes. In addition to eye homogenates, the activities of carboxylesterase 1 and 2 and peptidases were also confirmed in vitreous humor samples from humans and the 3 preclinical species. In general, the extent of in vitro hydrolytic activities of the tested hydrolases in monkeys better mimics those in humans after 24 hours of incubation. The results from this study will offer a better insight for understanding the pharmacokinetic principles of ophthalmic administration in the eyes. SIGNIFICANCE STATEMENT: This study investigated the activities of key hydrolases in the eye homogenates and vitreous humor from humans and preclinical species. The findings of the study provide an understanding of ocular drug metabolism and potentially contributes to ocular drug design and delivery.

Indexed as

EyeHydrolasesVitreous BodyAdultAnimalsFemaleHumansLiverMacaca fascicularisMaleMiddle AgedRabbitsSpecies SpecificitySwineSwine, MiniatureHydrolasesEye homogenatesHydrolasesOcular metabolismVitreous humor

Identifiers

PMID40896888
PMCPMC12597570

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.