Neuroprotective Effects of Human Serum Albumin Nanoparticles Loaded With Brimonidine on Retinal Ganglion Cells in Optic Nerve Crush Model

摘要

Purpose: We investigated the neuroprotective effect of human serum albumin nanoparticles (HSA-NPs) and their conjugation with brimonidine (HSA-Br-NPs) on retinal ganglion cells (RGCs) in optic nerve crush (ONC) model. Methods: We fabricated HSA-Br-NPs by ethanol precipitation, including 0.18% brimonidine (Br) and 3.5% human serum albumin (HSA) in HSA-Br-NP solution. We performed ONC and intravitreal injection in Spraguea??Dawley rats, which were divided into (1) Normal, (2) balanced salt solution (BSS)a??injected ONC, (3) HSA-NPa??injected ONC, (4) Br-injected ONC, and (5) HSA-Br-NPa??injected ONC groups. Survival of RGC was compared 5 and 14 days after procedures. A cell viability assay evaluated the amyloid-?2 (A?2)a??associated neuroprotective mechanism of HSA-NP. Results: The HSA-Br-NPs showed a narrow size distribution (152.8 ?± 51.1 nm) and a negatively charged surface (a??29.7 ?± 7.5 mV), releasing Br for 5 days. The percentages of RGC survival in the HSA-NP (52.6 ?± 3.3%), Br (58.0 ?± 4.2%), and HSA-Br-NP (63.5 ?± 7.1%) groups relative to Normal (100%) were significantly higher than in the BSS group (29.2 ?± 3.3%) 5 days after ONC (P 0.001). However, the HSA-Br-NP (38.1 ?± 3.6%) group showed significantly higher RGC density than the BSS (10.3 ?± 5.6%, P 0.001) or Br (18.6 ?± 3.9%, P = 0.006) group at 14 days. The HSA-NP injection reduced A?2 deposition in the RGC layer of ONC model, and a cell viability test showed that HSA-NP can inhibit A?2-induced RGC death. Conclusions: Human serum albumin nanoparticles showed neuroprotective potential by inhibiting A?2 deposition, and exerted a sustained therapeutic effect with the combined neuroprotective agent. Our results suggest the potential of HSA-Br-NP as a promising neuroprotective agent.