| First Author | Balne PK | Year | 2021 |
| Journal | Exp Eye Res | Volume | 207 |
| Pages | 108610 | PubMed ID | 33940009 |
| Mgi Jnum | J:322046 | Mgi Id | MGI:6741616 |
| Doi | 10.1016/j.exer.2021.108610 | Citation | Balne PK, et al. (2021) The functional role of decorin in corneal neovascularization in vivo. Exp Eye Res 207:108610 |
| abstractText | Our earlier decorin (Dcn) gene overexpression studies found that the targeted Dcn gene transfer into the cornea inhibited corneal angiogenesis in vivo using a rabbit model. In this study, we tested the hypothesis that anti-angiogenic effects of decorin in the cornea are mediated by alterations in a normal physiologic balance of pro- and anti-angiogenic factors using decorin deficient (Dcn(-/-)) and wild type (Dcn(+/+)) mice. Corneal neovascularization (CNV) in Dcn(-/-) and Dcn(+/+) mice was produced with a standard chemical injury technique. The clinical progression of CNV in mice was monitored with stereo- and slit-lamp microscopes, and histopathological hematoxylin and eosin (H&E) staining. Protein and mRNA expression of pro- and anti-angiogenic factors in the cornea were evaluated using immunofluorescence and quantitative real-time PCR, respectively. Slit-lamp clinical eye examinations revealed significantly more CNV in Dcn(-/-) mice than the Dcn(+/+) mice post-injury (p < 0.05) and AAV5-Dcn gene therapy significantly reduced CNV in Dcn(-/-) mice compered to no AAV5-Dcn gene therapy controls (p < 0.001). H&E-stained corneal sections exhibited morphology with several neovessels in injured corneas of the Dcn(-/-) mice than the Dcn(+/+) mice. Immunofluorescence of corneal sections displayed significantly higher expression of alpha-smooth muscle actin (alpha-SMA) and endoglin proteins in Dcn(-/-) mice than Dcn(+/+) mice (p < 0.05). Quantitative real-time PCR found significantly increased mRNA levels of pro-angiogenic factors endoglin (2.53-fold; p < 0.05), Vegf (2.47-fold; p < 0.05), and Pecam (2.14-fold; p < 0.05) and anti-angiogenic factor Vegfr2 (1.56-fold; p < 0.05) in the normal cornea of the Dcn(-/-) mice than the Dcn(+/+) mice. Furthermore, neovascularized Dcn(-/-) mice corneas showed greater increase in mRNA expression of pro-angiogenic factors endoglin (4.58-fold; p < 0.0001), Vegf (4.16-fold; p < 0.0001), and Pdgf (2.15-fold; p < 0.0001) and reduced expression of anti-angiogenic factors Ang2 (0.12-fold; p < 0.05), Timp1 (0.22-fold; p < 0.05), and Vegfr2 (0.67-fold; p > 0.05) compared to neovascularized Dcn(+/+) mice corneas. These gene deficience studies carried with transgenic Dcn(-/-) mice revealed decorin's role in influencing a physiologic balance between pro-and anti-angiogenic factors in the normal and injured cornea. We infer that the functional deletion of Dcn promotes irregular corneal repair and aggravates CNV. |
