Noninvasive Electroretinography Assessment of Intravitreal Sustained-Release Methotrexate Microimplants in Rabbit Eyes

Soumyarwit Manna, James J. Augsburger, Zelia M. Correa, Marwan F. Al-Rjoub, Marepalli B. Rao, Rupak K. Banerjee

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The purpose of this study is to noninvasively evaluate the safety and toxicity of a chitosan (CS) and polylactic acid (PLA)-based sustained-release methotrexate (MTX) intravitreal microimplant in normal rabbit eyes using electroretinography (ERG). Methods: PLA-coated CS-based microimplants containing 400 μg of MTX and placebo microimplants (without drug) were surgically implanted in the vitreous of the right and the left eyes, respectively, in each of the 8 New Zealand rabbits using minimally invasive technique. At each predetermined time points (days 5, 12, 19, and 33), ERG was conducted on 2 rabbits to evaluate the safety of the microimplants administered in each eye. ERG was carried out using 2 protocols, scotopic and photopic, on each eye prior to surgery (PS) and prior to euthanasia (PE) conditions. The safety of the microimplants was assessed using statistical analysis of the ERG data (B/A ratio analysis, oscillatory potential analysis, and Naka-Rushton analysis) and subsequently quantifying and comparing functional integrity of the retina between the PS and PE conditions of each eye. Results: Statistical analysis of the ERG data showed no change in retinal functional integrity because of the PLA-coated CS-based MTX microimplant and the placebo microimplant. ERG analysis also revealed absence of any evident bioelectrical dysfunction caused by the microimplants. Conclusion: ERGs were performed to determine whether the microimplants containing MTX and the placebo microimplants were associated with any profound retinal bioelectrical dysfunction that might be attributable to toxicity not apparent on histological studies of such eyes. The results shown in this report indicate that there were no such evident adverse effects of the microimplants or contained drug.

Original languageEnglish (US)
Pages (from-to)583-594
Number of pages12
JournalJournal of Ocular Pharmacology and Therapeutics
Volume32
Issue number9
DOIs
StatePublished - Nov 1 2016

Keywords

  • Electroretinogram
  • chitosan
  • intravitreal
  • methotrexate
  • polylactic acid
  • sustained drug delivery

ASJC Scopus subject areas

  • Ophthalmology
  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Noninvasive Electroretinography Assessment of Intravitreal Sustained-Release Methotrexate Microimplants in Rabbit Eyes'. Together they form a unique fingerprint.

Cite this