Effects Of Rosiglitazone,the PPAR-? Agonist,on Corneal Haze After PRK In Rabbits

Background Haze is the main factor of photorefractive keratectomy(PRK)on postoperative corneal transparency decline.The formation of haze after PRK is a process of corneal stromal cell fibrosis.In recent years,some studies found that peroxisome proliferater-activated receptor gamma(PPAR-y)agonist rosiglidone can inhibit ocular fibrosis,but the effect on haze is not clear.Objective To investigate the effect of PPAR-? agonist rosiglitazone on haze after PRK in rabbits.Observe the expressions of transforming grown facter-?1(TGF-?1),?-smooth muscle actin(a-SMA),atrix metalloproteinases-2(MMP-2).Methods 88 New Zealand white rabbits were selected,and the right eye was selected as the experimental eye,were randomly divided into experimental group and the blank control group.8 rabbits for blank control group,without any processing,the experimental group were under PRK surgery in the right eye,then randomly divided into 28?mol·L-1 rosiglitazone group,14?mol·L-1 rosiglitazone group,normal saline group,0.1%dimethyl sulfoxide(DMSO)+normal saline group,simple PRK group,each group had 16 rabbits.After 7 days and 28 days of PRK,8 rabbits were sacrificed in each group and 4 rabbits in the blank control group were sacrificed.Fantes was used to classify haze on day 7 and day 28 after PRK and recorded by anterior segmental photography.Anterior segment optical coherence tomography(AS-OCT)and hematoxylin-eosin(HE)staining were used to observe the healing of corneal.The corneal healing and the expressions of TGF-?1,?-SMA and MMP-2 were observed by hematoxylin-eosin staining and immunohistochemistry after 7 days and 28 days of PRK.Results Corneal epithelium in the operation group was healed on 3-4 days,and the difference was not statistically significant(F=0.47,P=0.76).Haze reached its peak around the 28 days.After 7 days and 28 days of PRK,the haze of 28?mol·L-1 rosiglitazone group were both the most light,followed by 14?mol·L-1 rosiglitazone group,significantly lighter than the other three experimental group(both P<0.05),there was no statistically significant difference between the normal saline group,0.1%DMSO+normal saline group and PRK group(both P>0.05);AS-OCT showed:7 days after surgery,corneal epithelial reflex was continuous,the shallow stromal layer was connected less tightly,and reflection was enhanced,28?mol·L-1 rosiglitazone group was the lightest,followed by 14?mol·L-1 rosiglitazone group,significantly lighter than the normal saline group and 0.1%DMSO+normal saline group and PRK group.At 4 weeks,the reflection of the shallow matrix layer was obviously enhanced,in the same order as before.HE staining showed that 7 days after surgery,corneal epithelium cells and fibroblasts hyperplasia of shallow layer matrix were hyperplasia,collagen fibers arranged disorder,28?mol·L-1 rosiglitazone group was the lightest,followed by 14?mol·L-1 rosiglitazone group,significantly lighter than the normal saline group,0.1%DMSO+normal saline group and PRK group.28 days after PRK,the above situation obviously increase,like the previous order on day 7.The expressions of TGF-?1??-SMA?MMP-2 in each group after 7 days and 28 days of PRK,28?mol.L-1 rosiglitazone group was the lightest,followed by 14?mol·L-1 rosiglitazone group,significantly lighter than the other three experimental group(both P<0.05),there was no statistically significant difference between the other three experimental group.(both P>0.05).Conclusion Rosiglitazone,a PPAR-? agonist,has an inhibitory effect on Haze after PRK in rabbits.The effect of high concentration is obvious at lower concentration,which may be mediated by the TGF-?1/Smad pathway.