ABSTRACT
Oxidative stress is closely associated with diabetes and can cause free radical accumulation and eventually lead to ocular surface tissue damage. The purpose of this study was to investigate peroxisome proliferator-activated receptor-γ (PPARγ) expression in the lacrimal gland (LG), meibomian gland, and cornea of diabetes-related dry eye mice and whether the PPARγ agonist rosiglitazone can alleviate the oxidative stress of the ocular surface, thereby improving the condition of diabetes-related dry eye. Quantitative RT-PCR (Q-PCR) showed that the PPARγ, catalase, glutathione peroxidase 3, and heme oxygenase-1 (HO-1) mRNA expression levels in the LG of diabetes-related dry eye mice decreased at 8 and 12 weeks. In addition, the increased levels of oxidative stress were confirmed by western blot. Although the mRNA expression levels of antioxidant enzymes in the cornea and meibomian gland decreased at 8 weeks, some of them recovered by 12 weeks. Rosiglitazone alleviated ocular surface damage and increased corneal sensitivity and tear production in diabetes-related dry eye mice. Moreover, the reactive oxygen species accumulation was reduced and the PPARγ, HO-1, and glutathione peroxidase 3 mRNA expression levels were increased in the LG. The PPARγ, HO-1, translocase of the outer membrane 20, and mitochondrial transcription factor A protein levels were also significantly increased. These results demonstrated that rosiglitazone reduced oxidative stress in the LG of diabetes-related dry eye mice, at least in part, by activating PPARγ to up-regulate antioxidant enzyme expression.
Subject(s)
Diabetes Mellitus , Dry Eye Syndromes , Mice , Animals , PPAR gamma/genetics , Rosiglitazone/pharmacology , Antioxidants/pharmacology , Oxidative Stress , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
The aim of this study was to explore the correlation between intraoperative hyperalgesia of the second eye and the dynamic changes of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels in aqueous humor (AH) of the second eye and whole blood after the first eye cataract surgery. A rabbit model of monocular phacoemulsification was established by administration of 0.3% levofloxacin. Whole blood and AH samples from non-surgical eyes in the experimental group (n =25) and second eye in the blank control group (n =15) were obtained and corneal sensitivity was examined after surgery (1, 3, 7, 14, and 21 days postoperatively). TNF-α and IL-1ß levels in AH and TNF-α mRNA and IL-1ß mRNA levels in whole blood were measured. In a clinical study, 30 patients who underwent bilateral phacoemulsification within 1 month were divided into six groups in accordance with the operation intervals (1, 3, 7, 10, 14, and 21days). TNF-α and IL-1ß levels in AH were measured at the beginning of surgery and intraoperative pain was assessed immediately after surgery. Corneal sensitivity (F =244.910, P <0.05), TNF-α and IL-1ß levels in AH (F =184.200, 82.900, P <0.05) of non-surgical eyes and in whole blood (F =272.800, 193.530, P <0.05) in the experimental group were significantly higher than the baseline levels after phacoemulsification. In the clinical study, NRS scores of second eye surgery were higher than those of the first eye(P =0.0025) and 19 (63.3%) patients reported more pain during the second eye surgery. TNF-α and IL-1ß concentrations in AH of the second eye were significantly higher than those of the first eye (F =123.60, P <0.05; F =59.60, P <0.05). In conclusion, within 1 month after the first eye phacoemulsification, higher pain sensitivity (hyperalgesia) exists in the second eye, which may be related to dynamic changes in TNF-α, IL-1ß levels in AH or whole blood.