September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Intravitreal injection vs. topical eye drop application of nanoparticles using a mouse model
Author Affiliations & Notes
  • Sara Wetzstein
    Ophthalmology, Emory, Decatur, Georgia, United States
  • Jana T Sellers
    Ophthalmology, Emory, Decatur, Georgia, United States
  • Kevin Donaldson
    Ophthalmology, Emory, Decatur, Georgia, United States
  • Gretchen Unger
    Genesegues, Inc., Chaska, Minnesota, United States
  • Shanu Markand
    Ophthalmology, Emory, Decatur, Georgia, United States
  • priyanka priyadarshani
    Ophthalmology, Emory, Decatur, Georgia, United States
  • Jeffrey H Boatright
    Ophthalmology, Emory, Decatur, Georgia, United States
    3Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, Georgia, United States
  • J M Nickerson
    Ophthalmology, Emory, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Sara Wetzstein, None; Jana Sellers, None; Kevin Donaldson, None; Gretchen Unger, Genesegues (E); Shanu Markand, None; priyanka priyadarshani, None; Jeffrey Boatright, None; J Nickerson, None
  • Footnotes
    Support  NIH R01EY016470, R01EY021592, P30EY006360, R01EY014026, Research to Prevent Blindness, Katz Foundation.
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1748. doi:
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      Sara Wetzstein, Jana T Sellers, Kevin Donaldson, Gretchen Unger, Shanu Markand, priyanka priyadarshani, Jeffrey H Boatright, J M Nickerson; Intravitreal injection vs. topical eye drop application of nanoparticles using a mouse model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1748.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : The purpose of this study was to test the hypothesis that intravitreal injection of nanoparticles (NPs) coated with hyaluronic acid (HA) impacts retinal morphology more than topical application in mouse eyes.

Methods : Male 129S2 mice at postnatal day 185 were subjected to either topical eye drop application (n=8) or intravitreal injection using a transcorneal route (n=8) of nanoparticles. Two hours post injection, mice were euthanized and eyes were enucleated with neutral buffered formalin with zinc fixation, sectioning, H&E staining, and imaging. A score system was employed using 3 separate blind examiners for evaluation of representative eye sections at 10X. Each section was graded for cracks, peeling, and histological damage. Evaluation followed a 4-point grading system for cornea, retina, lens, and an overall score, with 0=intact morphology, 1=light damage, 2=mild damage, and 3=heavy damage. A Mann-Whitney test was used to assess statistical significance between treatment groups.

Results : Histological analysis revealed that intravitreal injection significantly damaged overall eye morphology (Topical: 1.055; Intravitreal: 2.055, p<0.0002) with a lower score indicating more intact morphology. Intravitreal injected eyes were significantly damaged for the cornea (Topical: 0.670; Intravitreal: 1.915, p <0.0061), lens (Topical: 1.165; Intravitreal: 2.250, p <0.0025), and retina (Topical: 1.250; Intravitreal: 2.000, p <0.0146) when analyzed individually. More intravitreal eyes hemorrhaged (50%) compared with topical eyes (12.5%).

Conclusions : Our data support the hypothesis that intravitreal nanoparticle injection significantly impacts eye morphology. Topical drops had fewer lens fractures, better-attached retinas, straight irises, and undamaged corneal epithelium and endothelium in H&E sections. Thus, the adverse impact of intravitreal injections should be counterbalanced with the potential benefit of direct nanoparticle delivery.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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