Nanoparticle-mediated neuroprotection in a rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION)

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.