In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model

Shandiz Tehrani, R. Katherine Delf, William O. Cepurna, Lauren Davis, Elaine Johnson, John Morrison

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.

Original languageEnglish (US)
Article number4453
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

Optic Disk
Optic Nerve
Rodentia
Actins
Optic Nerve Diseases
Axons
Phalloidine
Cytochalasin D
Nerve Tissue
Retinal Ganglion Cells
Tubulin
Cytoskeleton
Ambulatory Surgical Procedures
Liquid Chromatography
Glaucoma
Mass Spectrometry
Animal Models
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model. / Tehrani, Shandiz; Delf, R. Katherine; Cepurna, William O.; Davis, Lauren; Johnson, Elaine; Morrison, John.

In: Scientific Reports, Vol. 8, No. 1, 4453, 01.12.2018.

Research output: Contribution to journalArticle

Tehrani, Shandiz ; Delf, R. Katherine ; Cepurna, William O. ; Davis, Lauren ; Johnson, Elaine ; Morrison, John. / In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{a5c0087ac28f49cd97ce4c22b3e4c588,
title = "In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model",
abstract = "Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.",
author = "Shandiz Tehrani and Delf, {R. Katherine} and Cepurna, {William O.} and Lauren Davis and Elaine Johnson and John Morrison",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-22737-4",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model

AU - Tehrani, Shandiz

AU - Delf, R. Katherine

AU - Cepurna, William O.

AU - Davis, Lauren

AU - Johnson, Elaine

AU - Morrison, John

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.

AB - Small molecule delivery to the optic nerve would allow for exploration of molecular and cellular pathways involved in normal physiology and optic neuropathies such as glaucoma, and provide a tool for screening therapeutics in animal models. We report a novel surgical method for small molecule drug delivery to the optic nerve head (ONH) in a rodent model. In proof-of-principle experiments, we delivered cytochalasin D (Cyt D; a filamentous actin inhibitor) to the junction of the superior optic nerve and globe in rats to target the actin-rich astrocytic cytoskeleton of the ONH. Cyt D delivery was quantified by liquid chromatography and mass spectrometry of isolated optic nerve tissue. One day after Cyt D delivery, anterior ONH filamentous actin bundle content was significantly reduced as assessed by fluorescent-tagged phalloidin labeling, relative to sham delivery. Anterior ONH nuclear counts and axon-specific beta-3 tubulin levels, as well as peripapillary retinal ganglion cell layer nuclear counts were not significantly altered after Cyt D delivery relative to sham delivery. Lastly, the surgical delivery technique caused minimal observable axon degeneration up to 10 days post-surgery. This small molecule delivery technique provides a new approach to studying optic neuropathies in in vivo rodent models.

UR - http://www.scopus.com/inward/record.url?scp=85044139838&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044139838&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-22737-4

DO - 10.1038/s41598-018-22737-4

M3 - Article

AN - SCOPUS:85044139838

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 4453

ER -