Bevacizumab and Rapamycin Can Decrease Corneal Opacity and Apoptotic Keratocyte Number following Photorefractive Keratectomy

Abstract

PURPOSE. We investigated the effects of bevacizumab and rapamycin on central corneal opacity and apoptotic keratocyte number after photorefractive keratectomy (PRK) followed by ultraviolet B (UV-B) irradiation. METHODS.A total of 60 right eyes of Sprague-Dawley rats in four groups (n ¼ 15 each) underwent PRK ablation to 80 lm with a 3-mm zone. Sponges soaked with 0.02% mitomycin C (MMC), 2.5% bevacizumab, 0.01% rapamycin, and balanced saline solution were applied for 2 minutes to these eyes in the MMC, bevacizumab, rapamycin, and control groups, respectively. At 3 weeks after PRK, all right eyes were exposed to 100 mJ/cm 2 UV-B irradiation. Biomicroscopy was used to determine the amount of haze, and TUNEL staining for apoptosis and histology were performed at 3, 6, and 12 weeks.RESULTS. Contrary to the results at 3 weeks, central corneal haze, and apoptotic keratocyte and keratocyte number decreased significantly in the MMC, bevacizumab, and rapamycin groups compared to the control group, and the keratocyte number was lower in the MMC group than the bevacizumab and rapamycin groups at 6 weeks (all P < 0.05). At 12 weeks, the apoptotic keratocyte number was lower in the MMC, bevacizumab, and rapamycin groups than the control group, and the keratocyte number was significantly lower in the MMC than the rapamycin and control groups (all P < 0.05).CONCLUSIONS. Intraoperative bevacizumab and rapamycin administration decreases central corneal haze and apoptotic keratocyte number after PRK. Bevacizumab and rapamycin may be safe alternatives to MMC during refractive surgery to prevent postoperative corneal opacity less affecting the keratocyte number. (Invest Ophthalmol Vis Sci. 2012; 53:7645-7653)

Rapamycin Inhibits the Production of Myofibroblasts and Reduces Corneal Scarring After Photorefractive Keratectomy

“…16 In the cornea it has been shown to modulate scarring, neovascularization, and inflammation. [17][18][19][20] In this study, we demonstrated that TGF-b activates the mTOR pathway in corneal stromal fibroblasts, and that rapamycin can inhibit their proliferation and modulate their transformation into myofibroblasts, hence reducing corneal scar formation.…”

“…Recently, another group evaluated the use of rapamycin alone or combined with bevacizumab in a rabbit model of photorefractive keratectomy. 17 Rapamycin was applied topically on the stromal bed just once. Their results demonstrated a modest beneficial effect from rapamycin, which they concluded was due partly to a reduction in keratocyte apoptosis.…”

The Antifibrosis Effects of Peroxisome Proliferator-Activated Receptorδon Rat Corneal Wound Healing after Excimer Laser Keratectomy

“…Standard Gill's II H & E staining was performed. The number of keratocytes was manually counted in five randomly selected nonoverlapping fields (×400) of the central cornea under microscope (Olympus BX50, Olympus, Tokyo, Japan) with a digital camera as previously described [ 26 ]. All H & E staining was performed at least three times to ensure that the results were consistent.…”

Rapamycin Prolongs the Survival of Corneal Epithelial Cells in Culture

“…In the cornea, mTOR plays an important role in regulating scarring, neovascularization, and inflammation14151617. Inhibiting mTOR with rapamycin can decrease corneal scarring in part by inhibiting the proliferation and differentiation of corneal myofibroblasts18.…”