Suppression of phagocytic cells in retinal disorders using amphiphilic poly(γ-glutamic acid) nanoparticles containing dexamethasone.
To investigate the potential of nanoparticles (NPs) composed of poly(γ-glutamic acid) conjugated with l-phenylalanine (γ-PGA-Phe NPs) for the treatment of retinal diseases, γ-PGA-Phe NPs (200nm) were tested with macrophages and microglia in vitro or by intravitreal administration into normal or pathological rat eyes. The anti-inflammatory effects of the NPs containing dexamethasone (DEX-NPs) were examined using qRT-PCR in vitro by counting activated microglia and Fluorogold-labeled retinal ganglion cells in the retinas under excitotoxicity or by counting TUNEL (+) photoreceptors in the detached retinas. The NPs were taken up efficiently by cultured macrophages or microglia. At day 7, 60-80% of the diffuse signal remained in the cytoplasm of these cells. In normal rat eyes, the NPs did not accumulate in the retinas and no inflammatory cells were recruited. Conversely, under pathological conditions, the NPs were localized in activated CD11b-positive cells in the retina. DEX-NPs suppressed the expression of TNFα and MCP-1 in cultured macrophages or microglia, the activation of microglia, the loss of retinal ganglion cells (RGCs) in excitotoxic retinas, and the number of TUNEL (+) photoreceptors in detached retinas. These data suggest that γ-PGA-Phe NPs can be a powerful tool for suppressing inflammatory cells in pathological conditions in the retina.
Department of Ophthalmology, Tohoku Graduate University School of Medicine, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574, Japan.
Morin
M
Ryu
Toru
T
Nakazawa
Takami
T
Akagi
Tatsuhide
T
Tanaka
Ryou
R
Watanabe
Masayuki
M
Yasuda
Noriko
N
Himori
Kazuichi
K
Maruyama
Toshihide
T
Yamashita
Toshiaki
T
Abe
Mitsuru
M
Akashi
Kohji
K
Nishida
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D012164:Retinal Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D003907:Dexamethasone