| Background Posterior capsular opacification (PCO) is the mos^common complication of modern cataract surgery. It has been reported that diabetic patients develop more severe PCO than nondiabetic patients after cataract surgery. The PCO in diabetic patients not only leads to the decrease of visual acuity after surgery, but also affects the treatment of diabetic patients with fundus examination, retinal photocoagulation and vitreous surgery. Echistatin as a member of the integrin family, early research found that, 10.0mg·L-1 echistatin could inhibit the postoperative lens epithelial cells (LECs) proliferation, migration and epithelial-mesenchymal transdifferentiation, and found PCO formation in diabetic rabbits with time gradually increased. LECs began to proliferate at 10 days (10d) postoperatively, and 6 weeks (6w) postoperatively reached a peak. However, the molecular mechanism of echistatin inhibition PCO formation in diabetic rabbit is still unclear.Purpose To observe the effect of disintegrin echistatin on integrin-linked kinase (ILK) and its downstream PI3-K/Akt and ERK1/2 signaling pathways in the formation of PCO in diabetic rabbit models.Methods (1) First,56 rabbits were injected alloxan via the ear margin vein to model diabetic rabbits; Secondly, they randomized to accept extracapsular lens extraction (right eyes). Thirdly, they were intraoperatively injected 0.2 ml distilled water (control group, n=28) or 10.0mg·L-1 echistatin (echistatin-treated group, n=28) into the anterior chamber. Last, each group was subdivided into 10d group (n=14) and 6w group (n=14) respectively. (2) After surgery the eyes of diabetic rabbits were treated by anti-inflammatory, anti-infection and pupil dilation. The cornea, anterior chamber and PCO grades were observed under slit lamp microscope. (3) 10d and 6w postoperatively, rabbits were sacrificed and right eyes were embedded in paraffin, LECs in posterior lens capsule and cornea and retina were observed with HE staining. (4) The expression of ILK in posterior capsule was analyzed by RT-PCR, immunohistochemistry and western blot respectively, at 10d and 6w after surgery. (5) The levels of Akt and ERK1/2 phosphorylation were determined by western blot at 10d and 6w postoperatively.Results (1) Postoperative observation:there was no significant difference of corneal edema and anterior chamber inflammation in the two diabetic rabbit groups after surgery (P> 0.05). (2) PCO grading:10d postoperatively, there was no significant difference in PCO grades of the two groups (P=0.057), but eyes number of PCO at grade 1 in echistatin-treated group (3 eyes) was significantly less than that of control group (8 eyes); 6w postoperatively, the grades of PCO in echistatin-treated group was significantly lower than control group (P=0.001). (3) Histopathological observation:the proliferation and migration of LECs in echistatin-treated group was significantly decreased than control group; there was no significant damage reaction with inducing by drug in cornea and retina of echistatin-treated group at postoperative early and late stage. (4) Expression of ILK:10d and 6w after surgery, the protein level of ILK in echistatin-treated group was significantly lower compared with control group (P=0.000 and 0.016), the level of ILK mRNA was also lower than control group (P=0.005 and 0.008 vs echistatin-treated group). (5) Activation of Akt and ERK1/2:10d and 6w postoperatively, the phosphorylation of Akt and ERK1/2 in echistatin-treated group were inhibited, p-Akt/Akt and p-ERK/ERK expression were significantly reduced than control group (P< 0.05).Conclusions Disintegrin echistatin could inhibit the occurrence and development of PCO in diabetic rabbits, which may be related to inhibit the expression of ILK and block its subsequent PI3-K/Akt and ERK1/2 signaling pathways. |
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