July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Pentablock Copolymer Dexamethasone Nanoformulations Induced Ocular Hypertension in Mice
Author Affiliations & Notes
  • Guorong Li
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Vibhuti Agrahari
    Department of Biopharmaceutical Sciences, Bernard J Dunn School of Pharmacy, Shenandoah University, Winchester, Virginia, United States
  • Iris Navarro
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Sina Farsiu
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Ashim K Mitra
    1School of Pharmacy, University of Missouri-Kansas City, Kansas City, Missouri, United States
  • W Daniel Stamer
    Ophthalmology, Duke Eye Center, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   Guorong Li, None; Vibhuti Agrahari, None; Iris Navarro, None; Sina Farsiu, None; Ashim Mitra, None; W Daniel Stamer, None
  • Footnotes
    Support  BrightFocus Foundation
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1659. doi:
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      Guorong Li, Vibhuti Agrahari, Iris Navarro, Sina Farsiu, Ashim K Mitra, W Daniel Stamer; Pentablock Copolymer Dexamethasone Nanoformulations Induced Ocular Hypertension in Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1659.

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

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Abstract

Purpose : To examine the effects of dexamethasone (DEX) encapsulated pentablock copolymer-based nanoparticles (NPs) (DEX.NPs) on intraocular pressure (IOP), plus function, behavior and ultrastructural changes in conventional outflow tissues in mice.

Methods : C57BL/6J mice were injected bilaterally with newly developed DEX.NPs or control nanoparticles (CON.NPs) in subconjunctival/periocular space once-twice/week for 2-8 weeks. IOP was measured twice/week with TonoLab Tonometer. Outflow facility was determined by iPerfusion system. Outflow tissue responses to IOP challenges (10-30 mmHg) in vivo were examined by Spectral Domain Optical Coherence Tomography (SD-OCT). Ultrastructural changes in outflow tissues were visualized by Transmission electron microscopy.

Results : The average IOP elevation in DEX.NPs treatment groups over 2 month period was 6.31 ± 0.23 mmHg compared to CON.NPs treatment groups (0.13 ± 0.13 mmHg). Outflow facility significantly decreased after 2-4 weeks DEX.NPs treatment (3.79±0.39 CON.NPs vs. 2.6±0.31 nl/min/mmHg DEX.NPs, p = 0.023). Using OCT, the Schlemm’s canal (SC) lumen demonstrated a higher resistance to collapse following increasing IOP gradients in the DEX.NPs treatment group compared to CON.NPs treatment group. The conventional outflow pathway displayed significant increase basement membrane deposits below the inner wall of SC, and increase collagen fibril content in the trabecular meshwork (TM) in DEX.NPs treated eyes compared to CON.NPs treated eyes.

Conclusions : Subconjunctival/periocular injection of DEX.NPs into mouse eyes induced sustained and IOP level controlled ocular hypertension; decreasing outflow facility; and TM ultrastructural changes that closely resemble human steroid induced ocular hypertension. Increased extracellular deposits in outflow tissues could lead to increase TM stiffness that prevented SC collapse at elevated IOPs.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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