8-hydroxy-2--deoxyguanosine and Corneal-Neovascularization

To evaluate the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) on experimental ocular chemical injury models.. We created ocular chemical injury models with 8-week-old BALB/c mice (n = 70) by applying 100% ethanol; the mice were then treated with 8-oxo-dG eye drops 10 and 5 mg/mL and phosphate-buffered saline (PBS) twice daily. After 7 days, clinical findings such as corneal integrity, clarity, and neovascularization were assessed. Histology, immunohistochemistry findings, and inflammatory cytokine levels using real-time polymerase chain reactions in the corneas of the mice were also analyzed.. Topical application of 8-oxo-dG eye drops resulted in a significant improvement of epithelial defects and clarity, dose dependently (each P < 0.001). Inflammatory cell infiltration and corneal stromal edema were also decreased in the 8-oxo-dG-treated mice compared with PBS-treated controls, based on hematoxylin and eosin staining. The expressions of F4/80 and neutrophil elastase-positive inflammatory cells and IL-1 and TNF-α cytokine levels were significantly reduced in the 8-oxo-dG group compared with the PBS group (each P < 0.01).. Topical 8-oxo-dG application showed an excellent therapeutic effect in ocular chemical injury models by suppressing inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Analysis of Variance; Animals; Burns, Chemical; Cornea; Corneal Injuries; Corneal Neovascularization; Corneal Stroma; Cytokines; Deoxyguanosine; Disease Models, Animal; Epithelium, Corneal; Ethanol; Eye Burns; Male; Mice; Mice, Inbred BALB C; Ophthalmic Solutions

Pigment epithelium-derived factor (PEDF) a glycoprotein that belongs to the superfamily of serine protease inhibitors, has been recently shown to be the most potent inhibitor of angiogenesis in the mammalian eye. However, which active domain of PEDF protein could be involved in its anti-angiogenic properties remains unknown. Therefore, in this study, we examined which PEDF-derived synthetic peptides could inhibit corneal neovascularization induced by chemical cauterization in vivo. Rats treated with topical application of PEDF protein had 31% less corneal neovascularization at day 7 after the injury than phosphate-buffered saline (PBS)-treated rats. P5-2 and P5-3 peptides (residues 388-393 and 394-400 of PEDF protein, respectively) significantly suppressed the corneal neovascularization after chemical cauterization at day 7, and its anti-angiogenic potential was almost equal to that of full-length PEDF protein. Further, full-length PEDF protein and P5-3 peptide significantly decreased 8-hydroxy-2'-deoxyguanosine and vascular endothelial growth factor (VEGF) levels in the corneal. Our present study suggests that PEDF-derived synthetic peptide, P5-3 could inhibit the corneal neovascularization induced by chemical cauterization in rats by suppressing VEGF expression via its anti-oxidative properties.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Topical; Angiogenesis Inhibitors; Animals; Cautery; Cornea; Corneal Injuries; Corneal Neovascularization; Deoxyguanosine; Disease Models, Animal; Eye Proteins; Male; Nerve Growth Factors; Rats; Rats, Sprague-Dawley; Serpins; Vascular Endothelial Growth Factor A