Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization

AIM： To evaluate whether trapping vascular endothelial growth factor-A（VEGF-A） would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model.METHODS： We established two groups of animals, one with non-dry eyes and the other with induced dry eyes.In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I（aflibercept）,subgroup II（dexamethasone） and subgroup III（phosphate buffered saline, PBS）. Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b＋ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas.RESULTS： Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas（all P 〈0.05）, but with no such effects in non-dry eyes. The anti-inflammatory and antiangiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas（all P 〈0.05）. The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreasedcompared with those in the PBS subgroup in the dry eye group.CONCLUSION： Compared with non-dry eye corneas,dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

Comparison of postoperative corneal changes between dry eye and non-dry eye in a murine cataract surgery model

AIM： To compare the effects of the surgical insult of cataract surgery on corneal inflammatory infiltration, neovascularization （NV） and lymphangiogenesis （LY） between the dry eye and non-dry eye in murine cataract surgery models.METHODS： We established two groups of animals, one with normal eyes （non-dry eye） and the second with induced dry eyes. In both groups, we used surgical insults to mimic human cataract surgery, which consisted of lens extraction, corneal incision and suture. After harvesting of corneas on the 9th postoperative day and immunohistochemical staining, we compared NV, LY and CD11b＋ cell infiltration in the corneas.RESULTS： Dry eye group had significantly more inflammatory infiltration （21.75%±7.17% r/s 3.65%±1.49%; P=0.049）. The dry eye group showed significantly more NV （48.21% ±4.02% ys 26.24% ±6.01% ; P =0.016） and greater levels of LY （9.27%±0.48% ys 4.84%±1.15%; P= 0.007）. In corneas on which no surgery was performed, there was no induction of NV in both the dry and non- dry group, but dry eye group demonstrated more CD11b＋ cells infiltration than the non-dry eye group （0.360%± 0.160% vs 0.023%±0.006%; P=0.068）. Dry eye group showed more NV than non-dry eye group in both topical PBS application and subconjunctival PBS injection （P= 0.020 and 0.000, respectively）.