New biological functions and applications of high-molecular-mass poly-gamma-glutamic acid.

Ultra-high-molecular-weight poly-gamma-glutamic acid (gamma-PGA) is a most promising biodegradable polymer that is produced by Bacillus subtilis (chungkookjang). Attractive properties of gamma-PGA are that it is water soluble, anionic, biodegradable, and edible. Development of gamma-PGA has pursued in terms of cosmetics/skin care, bone care, nanoparticle for drug delivery system, hydrogel, and so on. Very recently, our research has shown that gamma-PGA can be used as an immune-stimulating agent, especially at high molecular weight. This review presents the synthesis and production of high-molecular-weight gamma-PGA and its various applications in industrial fields.

Effects of ultra high molecular weight poly-gamma-glutamic acid from Bacillus subtilis (chungkookjang) on corneal wound healing.

Poly-gamma-glutamic acid (gamma-PGA) is a natural, edible polypeptide in which glutamate is polymerized via gamma-amide linkages. First, we assessed the eye irritancy potential of gamma PGA in rabbits. Additionally, we studied the effects of gamma-PGA on corneal wound healing, due to the anti inflammatory properties and water retaining abilities of gamma-PGA. In this study, the effects of gamma-PGA on corneal wound healing after an alkali burn were evaluated. Thirty eyes wounded by alkali burning in 30 white rabbits were divided into three groups: group A was treated with 0.1% 5000 kDa gamma-PGA for 2 days, group B was treated with 0.1% hyaluronic acid, and group C was not treated, as a control. The area of corneal epithelial defect was examined at 12, 24, 30, 36, 42, and 48 h after corneal alkali wounding to determine initial wound healing. We found that gamma-PGA promoted corneal wound healing, compared with controls, and showed similar effects to hyaluronic acid. These results indicate that gamma-PGA stimulates corneal wound healing by an anti inflammatory effect and enhancing cell migration and cell proliferation. gamma-PGA is a promising biomaterial that may be a substitute for hyaluronic acid in corneal wound healing treatment.

Direct detection of reactive nitrogen species in experimental autoimmune uveitis.

PURPOSE: Demonstrate unequivocally the generation of nitric oxide in experimental autoimmune uveoretinitis by electron spin resonance spectroscopy (ESR) using ferrous iron complex of N-methyl-D-glucamine dithiocarbamate, (MGD)(2)-Fe(2+), as a spin trap. METHODS: Experimental autoimmune uveitis was induced in Lewis rats, and at the peak of the intraocular inflammation, the animals received intravitreous injections of the spin trap. The retina and choroid dissected from the enucleated globes were subjected to ESR. Similarly, the retina and choroid obtained at the peak of experimental autoimmune uveo-retinitis (EAU) were placed in a vial containing luminal, and chemiluminescence was counted on a Packard liquid scintillation analyzer. RESULTS: The ESR three-line spectrum (g=2.04; a(N)=12.5 G) obtained was characteristic of the adduct [(MGD)(2)-Fe(2+)-NO]. The majority of this signal was eliminated by the inducible nitric oxide synthase (iNOS) specific inhibitor aminoguanidine injected inflamed retina was detected when compared with that of the non inflamed controls. The chemiluminescent activity was further increased two-fold by the addition of bicarbonate to the inflamed retina; the phenomenon is attributable only to the presence of a high steady-state concentration of peroxynitrite. CONCLUSIONS: The study shows an unequivocal presence of nitric oxide in EAU retina and choroid and the generation of peroxynitrite. High levels of these reactive nitrogen species generated in the inflamed retina and choroids are certain to cause irreversible tissue damage, especially at the susceptible sites such as photoreceptors.