June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Cross-Species and Cross-Age Comparison of Esterase Mediated Metabolism in Vitreous Humor: Human versus Rabbit, Dog and Monkey
Author Affiliations & Notes
  • Mayssa Attar
    Drug Safety Evaluation, Allergan, Irvine, CA
  • Jie Shen
    Drug Safety Evaluation, Allergan, Irvine, CA
  • Moon Kim
    Drug Safety Evaluation, Allergan, Irvine, CA
  • Que-Chau Radojicic
    Drug Safety Evaluation, Allergan, Irvine, CA
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5404. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Mayssa Attar, Jie Shen, Moon Kim, Que-Chau Radojicic; Cross-Species and Cross-Age Comparison of Esterase Mediated Metabolism in Vitreous Humor: Human versus Rabbit, Dog and Monkey. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5404.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose: Little is known regarding the enzymatic capabilities in vitreous humor across species and age groups. The objective of this study was to compare esterase mediated metabolism and identify any age effect in human vitreous humor relative to rabbit, dog and monkey vitreous humor.

Methods: Latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2α-1-isopropyl ester) was used as a prototype substrate to monitor esterase metabolism. Human vitreous humor was obtained from individual donors ranging in age from 67 to 86 years. Young and old vitreous humor was obtained from rabbit (<1 and >2 years old), dog (2-5 and >5 years old) and monkey (3-4 and > 5 years old). Metabolite formation was measured following incubation at 37°C of 500 μL vitreous humor and 6 μM latanoprost with timepoints taken at 0, 10, 20, 30 and 60 minutes. Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to quantify latanoprost disappearance and latanoprost acid formation.

Results: Latanoprost was metabolized to latanoprost acid in human and animal vitreous humor indicating esterases are active in vitreous humor. Rates of esterase metabolism were highest in human followed by rabbit, followed by monkey, followed by dog. Esterase metabolism appeared to decrease with increasing age except in rabbit. Latanoprost was stable when incubated in buffer for 60 minutes at 37°C.

Conclusions: Esterase mediated latanoprost metabolism is active in human and animal vitreous humor. Rate of esterase metabolism was highest in human as compared to all animals tested. Among the animal species tested rates of esterase metabolism in rabbit are most similar to human. Esterase metabolism tended to decrease with age.

Keywords: 763 vitreous • 592 metabolism • 503 drug toxicity/drug effects  
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×