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

초록

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 Sprague-Dawley rats, which were divided into (1) Normal, (2) balanced salt solution (BSS)-injected ONC, (3) HSA-NP-injected ONC, (4) Br-injected ONC, and (5) HSA-Br-NP-injected ONC groups. Survival of RGC was compared 5 and 14 days after procedures. A cell viability assay evaluated the amyloid-beta (A beta)-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 (-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 beta deposition in the RGC layer of ONC model, and a cell viability test showed that HSA-NP can inhibit A beta-induced RGC death. CONCLUSIONS. Human serum albumin nanoparticles showed neuroprotective potential by inhibiting A beta 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.

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