The Inhibitory Effect of Connective Tissue Growth Factor Neutralizing Antibody on Postoperative Fibrosis in a Rabbit Model of Trabeculectomy
Kiana Hassanpour1 *, Mozhgan Rezaei Kanavi2 , Narsis Daftarian2 , Azadeh Samaeili1 , Azadeh Doozandeh1 , Sasha Afsar-Aski1 , Fatemeh Suri1 , Hamid Ahmadieh1 , Mohammad Pakravan 3 , Hamed Esfandiari1
- Ophthalmic Research Center, Research institute for Ophthalmology and vision Scinece, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ocular Tissue Engineering Research Center, Research institute for Ophthalmology and vision Scinece, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Epidemiology Research Center, Research institute for Ophthalmology and vision Scinece , Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract: To compare the efficacy of subconjunctival injection of anti-connective tissue growth factor antibody anti-CTGF) in reducing the scar formation with mitomycin-C (MMC) and placebo in a rabbit model of trabeculectomy.
Methods: a total of 14 rabbits were included. Nine rabbits underwent trabeculectomy with subconjunctival injection of either anti-CTGF antibody, MMC, or BSS, each in 3 eyes, before peritomy. Anti-CTGF group received a repeated dose of the antibody 5 days after surgery. Nine rabbits were sacrificed on day 14; the globes were stained for hematoxylin & eosin, Masson’s Trichrome and immunohistochemistry for alpha-smooth muscle (α-SMA) actin. RNA extraction was performed on five eyes including without prior surgery, and operated eyes five hours and 5 days after trabeculectomy. MMC and BSS was injected after trabeculectomy in two eyes, respectively.
Results: The mean bleb area of the anti-CTGF, MMC and control groups was 3.8 ± 1.45, 5.9 ± 1.4, and 3.5 ± 1.9 mm2, respectively. The collagenous tissue was found to occupy the bleb by 13.7 %, 13.5%, and 18.5%, respectively. This ratio was significantly higher in the BSS group (P=0.04). Expression of CTGF mRNA 5 hours and 5 days in eyes with trabeculectomy were significantly more pronounced compared to the naïve eyes. Mean H-SCORE of ?-SMA-immune reactive cells calculated as the grade of staining multiplied by the percentage of immune stained cells was 14.6, 10.22, and 140.58, respectively. While the control eyes had a significantly higher score (Ps<0.001), anti-CTGF and MMC groups were comparable. (P=0.87).
Conclusion: Our results showed that the anti-CTGF resulted in a favorable bleb function and morphology. Histopathologic examinations demonstrated a significant reduction in collagenous tissue and myofibroblast cells.
