Topical rosiglitazone is an effective anti-scarring agent in the cornea.
Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas.
Flaum Eye Institute, University of Rochester, Rochester, New York, United States of America. huxlin@cvs.rochester.edu
Krystel R
KR
Huxlin
Holly B
HB
Hindman
Kye-Im
KI
Jeon
Jens
J
Bühren
Scott
S
MacRae
Margaret
M
DeMagistris
David
D
Ciufo
Patricia J
PJ
Sime
Richard P
RP
Phipps
D000199:Actins / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D002415:Cats; D002454:Cell Differentiation; D002478:Cells, Cultured; D002921:Cicatrix / Q000517:prevention & control*; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D057108:Corneal Wavefront Aberration / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D058628:Myofibroblasts / Q000187:drug effects / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000502:physiology; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects
D000199:Actins; D047495:PPAR gamma; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077154:Rosiglitazone