September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Nanoparticle-mediated neuroprotection in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)
Author Affiliations & Notes
  • Mary A Johnson
    Ophthal & Visual Science, Univ of Maryland Sch of Medicine, Baltimore, Maryland, United States
  • Yan Guo
    Ophthal & Visual Science, Univ of Maryland Sch of Medicine, Baltimore, Maryland, United States
  • Zara Mehrabyan
    Ophthal & Visual Science, Univ of Maryland Sch of Medicine, Baltimore, Maryland, United States
  • Manoj K. Mishra
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Siva Pramodh Kambhampati
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Kannan Rangaramanujam
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Neil Miller
    Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, United States
  • Steven L Bernstein
    Ophthal & Visual Science, Univ of Maryland Sch of Medicine, Baltimore, Maryland, United States
    Anatomy & Neurobiology, University of Maryland, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Mary Johnson, None; Yan Guo, None; Zara Mehrabyan, None; Manoj Mishra, Provisional Patent P12991-01 (P); Siva Pramodh Kambhampati, Provisional Patent P12991-01 (P); Kannan Rangaramanujam, Ashvattha Therapeutics (I), Orpheris Inc. (I), patents filed in US (#12/681,516), Canada (#2,701,291), European Union (#08835693.6), Japan (#2010-528216) and India (1247/ELNP/2010) (P), Provisional Patent P12991-01 (P), US patent (#12/797,657) and international PCT (PCT/US10/38068) (P); Neil Miller, None; Steven Bernstein, None
  • Footnotes
    Support  NIH grant RO1 EY015304
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Mary A Johnson, Yan Guo, Zara Mehrabyan, Manoj K. Mishra, Siva Pramodh Kambhampati, Kannan Rangaramanujam, Neil Miller, Steven L Bernstein; Nanoparticle-mediated neuroprotection in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION). Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : Polyamidoamine (PAMAM) 4-nanometer (nm) dendrimer nanoparticles are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells. In this study, we determined if dendrimers target the optic nerve (ON) lesion in our rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION). Additionally, we evaluated the neuroprotective ability of a dendrimer-linked anti-inflammatory agent, N-Acetyl cysteine (NAC).

Methods : Dendrimers were chemically linked to cyanine-5 fluorescent dye (D-Cy5) and injected systemically to evaluate D-Cy5 tissue accumulation in eye and optic nerve in our rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION). Neuroprotection by dendrimer linked to NAC (D-NAC) was evaluated by retinal ganglion cell (RGC) counts and by visual evoked potential (VEP) in rNAION-induced animals that were treated with either D-NAC or vehicle.

Results : Cy5-dendrimers selectively target the ischemic lesion after rNAION induction, accumulating in astrocytes and circulating macrophages. Systemic D-NAC administration post-rNAION induction resulted in statistically significant RGC survival (p < 0.015) and VEP amplitude preservation at 2 weeks post induction (p < 0.04) compared with vehicle controls.

Conclusions : Systemic dendrimer-linked therapeutics may be used to dramatically increase the selective intracellular concentration of neuroprotective agents and provide a powerful new, targeted approach to NAION treatment.

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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