July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Intravitreal Connective Tissue Growth Factor Neutralizing Antibody Reduces Subretinal Fibrosis Associated with Experimental Choroidal Neovascular Membrane
Author Affiliations & Notes
  • Hamid Ahmadieh
    Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Narsis Daftarian
    Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Shirin Rohani
    Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Mozhgan Rezaei Kanavi
    Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Fatemeh Suri
    Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Mehraban Mirrahimi
    Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran (the Islamic Republic of)
  • Ali Hafezi-Moghadam
    Molecular Biomarkers Nano-Imaging Laboratory, Department of Radiology, Harvard Medical School, Boston, Massachusetts, United States
  • Zahra-Soheila Soheili
    National Institute of Genetic Engineering and Biotechnology, Tehran, Iran (the Islamic Republic of)
  • Footnotes
    Commercial Relationships   Hamid Ahmadieh, None; Narsis Daftarian, None; Shirin Rohani, None; Mozhgan Rezaei Kanavi, None; Fatemeh Suri, None; Mehraban Mirrahimi, None; Ali Hafezi-Moghadam, None; Zahra-Soheila Soheili, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2978. doi:
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      Hamid Ahmadieh, Narsis Daftarian, Shirin Rohani, Mozhgan Rezaei Kanavi, Fatemeh Suri, Mehraban Mirrahimi, Ali Hafezi-Moghadam, Zahra-Soheila Soheili; Intravitreal Connective Tissue Growth Factor Neutralizing Antibody Reduces Subretinal Fibrosis Associated with Experimental Choroidal Neovascular Membrane. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2978.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Connective tissue growth factor (CTGF) is a potent mitogen for angiogenesis-related fibrosis. This experimental study was performed to evaluate if CTGF is elevated after laser induced choroidal neovascular membrane (CNV) formation and whether intravitreal anti-CTGF without and with intravitreal bevacizumab (IVB) may have any effect on the CNV- associated subretinal fibrosis.

Methods : In adherence to the ARVO regulations, CNV was induced by laser spots in the right eye retinas of 64 pigmented rats. qRT-PCR was performed on sclerochoroidal tissues from 24 rats before and at seven different intervals after laser application. The remaining 40 rats were randomly divided into four groups: Group A received intravitreal injection of 2µl of the 50µg/ml anti-CTGF, group B received 2µl of 25mg/ml intravitreal bevacizumab (IVB) and group C received 1µ intravitreal anti-CTGF plus 1µl IVB. Group D with laser application did not receive any injection (the control group). After two weeks, double immunohistochemistry was performed by isolectin B4 and anti-collagen type1 on the sclerochoroidal flat-mounts. Masked measurement of the fluorescent images of the CNV and CNV- associated subretinal fibrosis areas was performed using the image J software.

Results : Ctgf mRNA level was significantly increased from three hours after laser induction to maximum level in 24 hours and remained significantly higher than the control level up to 15th day. Means of CNV- associated subretinal fibrosis areas in three treatment groups (A, B, C) were significantly less than control group (P<0.001, <0.05, <0.001, respectively). For groups A and C, mean CNV- associated subretinal areas were also significantly less than group B (P<0.05 and <0.01, respectively).

Conclusions : Inhibition of CTGF leads to significant reduction of subretinal fibrosis associated with laser induced CNV. The clinical implication of this finding needs further studies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Columns from left to right: Isolectin B4 (green fluorescence) for labeling vascular component of CNVs, anti-collagen (red fluorescence) for labeling fibrosis component of CNVs, and merged photos of double staining for isolectin and anti-collagen
type1. Rows from top to bottom: Group D (controls), Group A (anti-CTGF), Group B (IVB) and Group C (anti-CTGF+IVB).

Columns from left to right: Isolectin B4 (green fluorescence) for labeling vascular component of CNVs, anti-collagen (red fluorescence) for labeling fibrosis component of CNVs, and merged photos of double staining for isolectin and anti-collagen
type1. Rows from top to bottom: Group D (controls), Group A (anti-CTGF), Group B (IVB) and Group C (anti-CTGF+IVB).

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