Anti-Angiogenic and Anti-Inflammatory Effects of SERPINA3K on Corneal Injury

Abstract

SERPINA3K is a member of the serine proteinase inhibitor (SERPIN) family. Here we evaluated the therapeutic effects of SERPINA3K on neovascularization and inflammation in a rat cornea alkali burn model that is commonly employed to study corneal wounding. Topical treatment of the injured rat cornea with SERPINA3K (20 µg/eye/day) for 7 days significantly decreased the neovascular area, compared with the groups treated with BSA or PBS. The SERPINA3K treatment also ameliorated the corneal inflammation as evaluated by the inflammatory index. Furthermore, SERPINA3K enhanced the recovery of corneal epithelium after the alkali injury. Toward the mechanism of action, SERPINA3K down-regulated the expression of the pro-angiogenic and pro-inflammatory factors, vascular endothelial growth factor and tumor necrosis factor-α and up-regulated the expression of the anti-angiogenic factor, pigment epithelium-derived factor. SERPINA3K specifically inhibited growth of vascular endothelial cells. Meanwhile, SERPINA3K significantly up-regulated the expression of EGFR in the corneal epithelium. These findings suggest that SERPINA3K has therapeutic potential for corneal inflammation and NV.

Corneal Neovascularization and Treatment: Review

“…86 Netrin-1 ve 4 ile SERPINA3K'de kombine etkili tedavi sağlayan yeni ajanlardandır. 87,88 Doğal bir antianjiyojenik faktör olan PEDF sekresyonunu artırır ve VEGF sekresyonunu baskılar. 89 Han ve ark.nın çalışmasında, alkali yanık modelinde 10 gün sonra başlanan netrin-1'in korneal NV'yi engellediği, antiapoptotik, antiinflamatuar etkilerinin olduğu ve epitel iyileşmesini hızlandırdığı gösteril-miştir.…”

Nanotechnology in Corneal Neovascularization Therapy—A Review

“…A similar study evaluated the effects of SERPINA3K, a natural antiangiogenic protein, 48 on corneal angiogenesis. Similar to the experiment described above, mice were subjected to an alkali burn and then treated with either a PBS control or SERPINA3K eye drop solution.…”

“…Eight days after alkali burn, the area of corneal NV was smaller in mice treated with SERPINA3K, and the cornea appeared more transparent and with less edema compared to control mice. 48 A Western blot analysis of the cornea performed 8 days after alkali burn showed that mice treated with the SERPINA3K expressed much lower levels of VEGF and higher levels of PEDF. 48 From these data, it is clear that netrin-1 and SER-PINA3K are two factors that show considerable promise in the inhibition of corneal angiogenesis.…”

KH902, a Recombinant Human VEGF Receptor Fusion Protein, Reduced the Level of Placental Growth Factor in Alkali Burn Induced-Corneal Neovascularization

“…Experimental corneal NV allows the clear visualization of abnormal vascular growth and shows no natural regression, making this an attractive model in which to study vessel regression. The corneal alkali burn model is a well-established model of corneal NV, corneal epithelial defects, prominent corneal inflammation, and reduced corneal transparency [2,3]. It is widely used to study the mechanism of and investigate therapies for inflammation and angiogenesis, due to well accessible position for observation, and the relatively immune-privileged status of the cornea.…”