Polydopamine nanoparticles attenuate retina ganglion cell degeneration and restore visual function after optic nerve injury

J Nanobiotechnology. 2021 Dec 20;19(1):436. doi: 10.1186/s12951-021-01199-3.

Abstract

Background: Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs.

Results: The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function.

Conclusions: The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.

Keywords: Drug delivery; Optic nerve injury; Polydopamine nanoparticle; Reactive oxygen species scavenging; Retina ganglion cell.

MeSH terms

  • Animals
  • Brimonidine Tartrate / chemistry
  • Brimonidine Tartrate / pharmacology
  • Brimonidine Tartrate / therapeutic use
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Indoles / chemistry
  • Indoles / pharmacology
  • Indoles / therapeutic use*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Optic Nerve Injuries / pathology*
  • Polymers / chemistry
  • Polymers / pharmacology
  • Polymers / therapeutic use*
  • Reactive Oxygen Species / chemistry
  • Retina / drug effects
  • Retina / physiology
  • Retinal Degeneration / drug therapy*
  • Retinal Degeneration / pathology
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism
  • Transcriptome / drug effects

Substances

  • Indoles
  • Polymers
  • Reactive Oxygen Species
  • polydopamine
  • Brimonidine Tartrate
  • Hydrogen Peroxide
  • Nitric Oxide Synthase Type II