title: RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.
abstract: Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50μl, 5μg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases.
authors: Inserm, U968, 17, rue Moreau, 75012 Paris, France; UPMC université Paris 06, UMR_S968, institut de la vision, 17, rue Moreau, 75012 Paris, France; CNRS, UMR_7210, 17, rue Moreau, 75012 Paris, France; Centre hospitalier national d'ophtalmologie des Quinze-Vingts, 28, rue de Charenton, 75012 Paris, France; Faculté des sciences pharmaceutiques et biologiques, laboratoire de toxicologie, Sorbonne Paris Cité, université Paris Descartes, 4, avenue de l'Observatoire, Paris, France.
authors: F
authors: F
authors: Brignole-Baudouin
authors: J M
authors: JM
authors: Warnet
authors: D
authors: D
authors: Barritault
authors: C
authors: C
authors: Baudouin
mesh_terms: D000818:Animals; D003316:Corneal Diseases / Q000188:drug therapy* / Q000473:pathology; D003320:Corneal Ulcer / Q000517:prevention & control; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005126:Eye Burns / Q000188:drug therapy / Q000473:pathology; D005355:Fibrosis / Q000517:prevention & control; D006025:Glycosaminoglycans / Q000627:therapeutic use*; D009883:Ophthalmic Solutions / Q000627:therapeutic use*; D011817:Rabbits; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D006025:Glycosaminoglycans; C533322:OTR4120; D009883:Ophthalmic Solutions
keywords: Alkali burn; Brûlure; Cicatrisation; Corneal ulcers; Heparan sulfate mimetic; Mimétique de sulfate d’héparane; RGTA; Ulcère de cornée; Wound healing