title: Corneal stroma PDGF blockade and myofibroblast development.
abstract: Myofibroblast development and haze generation in the corneal stroma is mediated by cytokines, including transforming growth factor-beta (TGF-beta), and possibly other cytokines. This study examined the effects of stromal PDGF-beta blockade on the development of myofibroblasts in response to -9.0 diopter photorefractive keratectomy in the rabbit. Rabbits that had haze generating photorefractive keratectomy (PRK, for 9 diopters of myopia) in one eye were divided into three different groups: stromal application of plasmid pCMV.PDGFRB.23KDEL expressing a subunit of PDGF receptor b (domains 2-3, which bind PDGF-B), stromal application of empty plasmid pCMV, or stromal application of balanced salt solution (BSS). The plasmids (at a concentration 1000ng/microl) or BSS was applied to the exposed stroma immediately after surgery and every 24h for 4-5 days until the epithelium healed. The group treated with pCMV.PDGFRB.23KDEL showed lower alphaSMA+ myofibroblast density in the anterior stroma compared to either control group (P<or=0.001). Although there was also lower corneal haze at the slit lamp at one month after surgery, the difference in haze after PDGF-B blockade was not statistically significant compared to either control group. Stromal PDGF-B blockade during the early postoperative period following PRK decreases stromal alphaSMA+ myofibroblast generation. PDGF is an important modulator of myofibroblast development in the cornea.
authors.affiliation: Cole Eye Institute, The Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Harmeet
authors.initials: H
authors.lastname: Kaur
authors.forename: Shyam S
authors.initials: SS
authors.lastname: Chaurasia
authors.forename: Fabricio W
authors.initials: FW
authors.lastname: de Medeiros
authors.forename: Vandana
authors.initials: V
authors.lastname: Agrawal
authors.forename: Marcella Q
authors.initials: MQ
authors.lastname: Salomao
authors.forename: Nirbhai
authors.initials: N
authors.lastname: Singh
authors.forename: Balamurali K
authors.initials: BK
authors.lastname: Ambati
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wilson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003318:Corneal Opacity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D018903:Photorefractive Keratectomy / Q000009:adverse effects; D010957:Plasmids; D011817:Rabbits; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000199:Actins; D020797:Receptor, Platelet-Derived Growth Factor beta