Aims/hypothesis. The healing of corneal epithelial wounds is often delayed in individuals with diabetes. The effect of the combination of a substance P-derived tetrapeptide (phenylalanine-glycine-leucinemethionine amide, or FGLM-NH 2 ) and insulin-like growth factor-1 (IGF-1) on corneal epithelial wound healing was investigated in rats with streptozotocininduced diabetes. Methods. The corneal epithelium of diabetic and nondiabetic rats was removed, and the animals were treated by the application of eye drops containing FGLM-NH 2 and IGF-1, or vehicle alone as a control, six times a day for 3 days. The area of the corneal epithelial wound was measured at various times up to 72 h after removal of the corneal epithelium.Results. The rate of corneal epithelial wound healing was slower in diabetic rats treated with vehicle than in non-diabetic rats. However, the rate of wound closure in diabetic rats treated with FGLM-NH 2 and IGF-1 was markedly increased compared with that in diabetic rats treated with vehicle. The wound healing process seemed similar in normal rats and in diabetic rats treated with FGLM-NH 2 and IGF-1. Conclusion/interpretation. The combination of FGLM-NH 2 and IGF-1 promotes corneal epithelial wound healing in diabetic rats, suggesting that such a treatment might prove effective in humans with diabetic keratopathy. [Diabetologia (2003) 46:839-842]

ABSTRACT:Precipitation polymerization of acrylamide derivatives in water resulted in the formation of monodisperse submicron particles. Repetitive seeded polymerizations using the product of precipitation polymerization or precipitation polymerization in ethanol-water media gave larger monodisperse particles. Especially, the latter was very effective for the preparation of micro-size particles.KEY WORDS Hydrogel / Microsphere / Precipitation Polymerization / Seeded Polymerization / Swelling / Hydrogel is a subject of great interest in these days due to its characteristic swellingdeswelling behavior in response to changes of temperature, pH, medium components, etc. and applications based on this character in medical, agricultural, and industrial fields. In many cases, quick and uniform responses are necessary for successful applications. The rate of response is inversely proportional to the square of its size. 1 Therefore, hydrogels are often used in small pieces, fine filaments, or thin films. Small pieces of hydrogels are usually prepared by crashing a bulk of gel or by inverse suspension polymerizations. 2 • 3 The particles given by inverse suspension polymerization have a diameter in the range of IO to 100 µm and not necessarily monodisperse.Recently, smaller and monodisperse microspheres were prepared by a novel precipitation polymerization by Pelton and Chibante. 4 They polymerized N-isopropyl acrylamide with N,N' -methylenebisacrylamide in water at 70°C. As the polymerization temperature was much higher than the lower critical solution temperature (LCST) of resulting polymer, ca. 35°C, the reaction accompanied precipitation of polymers and produced a dispersion of polymer particles with submicron diameter. Some other acrylamide derivatives also give polymers with their specific LCSTs. For example, the polymers of acryloyl pyrrolidine and acryloyl piperidine have their LCSTs at 50°C and 5°C, respectively. We have used such monomers with styrene to prepare latex particles having shells composed of them, which exhibited reversible expansion-shrinkage with changing temperature. 5 • 6 The precipitation polymerization of these acrylamide derivatives was found to result in the formation of monodisperse submicron hydrogel microspheres.The most suitable size of hydrogel microspheres in their applications differs from case to case. Submicron-size might be too small to treat in many cases. The smaller the particles t Present address: Mitsui

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Topical application of the combination of SP and IGF-1 improved both corneal epithelial barrier function and epithelial wound healing in an animal model of neurotrophic keratopathy.

The aim of this study was to establish a method for analysis of tear film stability and thereby to investigate the effects of lubricants on corneal surface regularity and corneal epithelial damage in anesthetized rabbits with the eye held open. Saline-instilled and noninstilled eyes manifested a time-dependent increase in the corneal surface regularity index (SRI). In contrast, 0.1% hyaluronic acid (HA) prevented the increase in the SRI for up to 20 min after instillation. Methylene blue uptake into the damaged cornea was significantly greater in eyes that received saline than in those treated with HA. Whereas eyes instilled with 0.5% methylcellulose (MC) or 0.35% sodium carboxymethylcellulose (CMC) manifested an increase in the SRI similar to that apparent in those that received saline, 1.0% chondroitin sulfate (CS) prevented the increase in the SRI for up to 10 min after instillation. In conclusion, we have established a method for analysis of tear film stability in rabbits. Our results suggest that tear film stability is closely related to corneal surface damage and that topical instillation of 0.1% HA or 1.0% chondroitin sulfate warrants further investigation as a potential treatment for patients with dry eye.