June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Delivery of Dexamethasone from Novel Pentablock Copolymer-Based Nanoformulation Promotes Prolonged Secretion of myocilin from Human Trabecular Meshwork Cells
Author Affiliations & Notes
  • Guorong Li
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Vibhuti Agrahari
    University of Missouri - Kansas City, Kansas, Missouri, United States
  • Vivek Agrahari
    University of Missouri - Kansas City, Kansas, Missouri, United States
  • Abhirup Mandal
    University of Missouri - Kansas City, Kansas, Missouri, United States
  • Ashim K Mitra
    University of Missouri - Kansas City, Kansas, Missouri, United States
  • W Daniel Stamer
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Guorong Li, None; Vibhuti Agrahari, None; Vivek Agrahari, None; Abhirup Mandal , None; Ashim Mitra, None; W Daniel Stamer, None
  • Footnotes
    Support  BrightFocus Foundation (G2015100); National Institutes of Health grant R01EY09171 and R01EY010659.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4446. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Guorong Li, Vibhuti Agrahari, Vivek Agrahari, Abhirup Mandal, Ashim K Mitra, W Daniel Stamer; Delivery of Dexamethasone from Novel Pentablock Copolymer-Based Nanoformulation Promotes Prolonged Secretion of myocilin from Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4446.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : To examine the effect of dexamethasone-loaded nanoparticles (Dex.NPs) on secretion of myocilin from primary cultures of human trabecular meshwork (HTM) cells over time.

Methods : Dex.NPs were formulated by entrapping Dex in novel pentablock copolymers. Five confluent HTM cell strains isolated from five different individual human donor eyes were treated with one application of 1mg/ml Dex.NPs or control.NPs. Cells were treated with Dex (100 nM) for 4 weeks as a positive control. Cell culture supernatants were collected/replaced on day 2, and then once/week with fresh media containing 1% FBS for 12 weeks. Myocilin content in the supernatant was monitored by Western blot, while cell viability and cytotoxicity were determined by WST-1 and LDH.

Results : Myocilin secretion from HTM cells increased during the first week of treatment with either 100 nM Dex (3.15±0.9-fold, p=0.023) or Dex.NPs (2.91±0.86-fold, p=0.048). Peak myocilin secretion occurred between weeks 3 and 6 for 100 nM Dex-treated cells (5-9-fold), compared to 4-6-fold increase for Dex.NPs cells. At week 7, myocilin levels dropped (<2-fold), and then were back to normal by week 8 in 100 nM Dex-treatment group. In contrast, myocilin secretion consistently stayed higher than 2-fold in Dex.NP group throughout the 12 week examination period. Additionally, none of Dex 100 nM, control.NP, or Dex.NP-treated cells showed signs of cytotoxicity to long-term treatment.

Conclusions : Our in vitro study showed that Dex.NPs have slow, steady, safe and long-term effects on secretion of myocilin from cultured HTM cells after a single treatment, validating usefulness of this novel NP preparation for drug delivery purposes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

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.

×