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Jayter S. Paula, Juliana L. Ferreira, Carolina M. Modulo, Roberta Cannellini, Lorena C. Vieira, Leandra N. Ramalho, Sergio B. Garcia, Armado S. Cunha; Effects of Rosmarinic Acid on Experimental Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2520.
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© ARVO (1962-2015); The Authors (2016-present)
Filtration failure due to excessive subconjunctival scarring remains a problem frequently observed after glaucoma surgery. Rosmarinic acid (RA) is a naturally occurring polyphenol, found in species of the subfamily Nepetoideae (Lamiaceae), with anti-inflammatory and anti-fibrotic activities. The aim of this study was to investigate the effect of RA on the wound healing process in a rabbit model of glaucoma filtration surgery.
Ten New Zealand rabbits underwent an experimental trabeculectomy and were randomly allocated to two treatment groups: group A - treated with subconjunctival injections of 0.3 ml RA (15 mg/ml; n=5); and group B - treated with subconjunctival injections of 0.3 ml PBS (n=5), given every 3 days, for 14 days. The in vivo effect of RA was investigated by measuring the intraocular pressure (IOP, with Tonopen) and bleb area (using Moorfields bleb grading system), and by immunohistological analysis of fibroblastic alpha-actin. Quantitative real time RT-PCR was used to evaluate the expression of type I collagen (COL1A1) and TGF-beta. Vascularization was studied by counting histological blood vessels at the surgical site and by vessel quantification in chicken chorioallantoic membrane (CAM; n=12).
Eyes of group A showed slightly, but not significantly, greater reductions of IOP (-1.4±0.3 vs -0.8±0.3 mmHg; P =0.226), and significantly higher bleb area scores (3.6±0.2 vs 1.8±0.2; P =0.004) when compared with group B. Expression of COL1A1 (P=0.028), TGF-beta (P=0.028), as well as the proportion of alpha-actin immunostaining fibroblasts (P=0.029) were significantly higher in group A than group B (Mann Whitney U test). However, RA treatment resulted in a significant reduction of blood vessels density (19.5±1.9 vs 11.5±1.4, for group A and B, respectively; P= 0.0286) and of the CAM vessels proportion (-45.7± 4.8%, compared to controls; P=0.008).
This study demonstrated that RA treatment was associated with increasing expression of fibrotic factors related to the subconjunctival scarring process in the experimental glaucoma surgery. However, once RA was able to decrease vascularization, it should be mainly considered as a potential anti-neovascular agent in further angiogenesis studies.
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