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S. E. Wilson, H. Kaur, S. S. Chaurasia, F. W. Medeiros, V. Agrawal, M. Q. Salomao, N. Singh, B. K. Ambati; Corneal Stromal PDGF Receptor Expression, PDGF Blockade and Modulation of Myofibroblast Development. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2553.
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To analyze platelet-derived growth factor (PDGF) receptor expression in myofibroblasts and the effect of PDGF receptor blockade on the development of myofibroblasts associated with development of stromal haze in response to -9 diopter photorefractive keratectomy in rabbits.
Immunohistochemistry for PDGF receptor- (PDGFR-) was performed in rabbit corneas at one month after haze generating -9 diopter photorefractive keratectomy (PRK). Rabbits that had - 9 diopter PRK in one eye were also divided into three different groups: stromal application of plasmid pCMV.PDGFRB.23KDEL expressing a subunit of PDGF receptor β (domains 2-3, which bind PDGF-β), stromal application of empty plasmid pCMV, or stromal application of balanced salt solution (BSS). The plasmids (at a concentration 1000 ng/µl) or BSS were applied to the exposed stroma immediately after surgery and every 24 hours for 4-5 days until the epithelium healed. At 4 weeks after surgery corneas were graded for haze at the slit lamp and myofibroblast density in corneal sections was determined by immunohistochemistry for smooth muscle actin (SMA).
PDGF receptors were expressed at high levels in myofibroblasts. After gene transfer, the group treated with pCMV.PDGFRB.23KDEL plasmid showed low SMA+ myofibroblast density in the anterior stroma compared to either control group (P≤ 0.001). Although there was also lower corneal haze at the slit lamp at one month after surgery, the difference in haze after PDGF-β blockade was not statistically significant compared to either control group.
PDGF receptor is expressed in corneal myofibroblasts. Stromal PDGF-β blockade during the early postoperative period following PRK profoundly decreases stromal SMA+ myofibroblast generation. However, since significant haze is still present, we hypothesize that PDGF modulates later events in myofibroblast development, such as the transition from vimentin+ to SMA+ myofibroblast.
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