May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Glaucomatous Changes in Two Rodent Models Involving Overexpression of TGFß in the Eye
Author Affiliations & Notes
  • J. V. Robertson
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • E. Golesic
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • J. Gauldie
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • J. West-Mays
    Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships J.V. Robertson, None; E. Golesic, None; J. Gauldie, None; J. West-Mays, None.
  • Footnotes
    Support NIH Grant EY015006-01
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5904. doi:
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      J. V. Robertson, E. Golesic, J. Gauldie, J. West-Mays; Glaucomatous Changes in Two Rodent Models Involving Overexpression of TGFß in the Eye. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5904.

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

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Abstract

Purpose:: Elevated levels of active transforming growth factor beta (TGFß) have been shown to be associated with multiple fibrotic diseases including pathologies of the eye. Glaucoma, commonly associated with high intraocular pressure concomitant with retinal detachment and ganglion cell death, has also been correlated with elevated levels of active TGFß. Our objective was to use two rodent models which overexpress TGFß in the eye to examine the role(s) that it plays in inducing glaucomatous changes.

Methods:: The transgenic mouse line expressing active TGFß1 in lens (under the αA crystallin promoter) was used to examine the long term effects of TGFß1 overexpression with respect to glaucomatous changes. Animals older than 4 months of age were sacrificed, enucleated and eyes were examined for gross anatomy, general histology and optic nerve thickness. Additionally, female Sprague Dawley rat eyes were injected with recombinant adenovirus containing active porcine TGFß1(AdTGFß1) or a reporter gene, LacZ (AdLacZ). Intraocular pressure measurements were taken weekly for one month at which time eyes were enucleated and the duration of transgene expression and general ocular histology were examined.

Results:: Gross morphology of murine transgenic eyes demonstrated larger globe size, smaller optic nerve diameter and retinal abnormalities compared to their wildtype littermates. Rat eyes injected with AdTGFß1 showed a statistically significant increase of IOP at 22 days post injection, which surprisingly resolved back to control levels by day 29. LacZ transgene expression was also shown to be present at day 29. Retinas of AdTGFß1 injected eyes showed minimal alterations in structure; however anterior subcapsular cataract formation was prominent.

Conclusions:: Chronically increased levels of TGFß1, in a transgenic model, has a profound effect on retinal morphology and optic nerve thickness. Our AdTGFß model has also shown that while IOP is elevated in response to TGFß after 3 weeks, the fact it returns to normal at 4 weeks suggests that mechanisms are in place to combat the initial effects of TGFß on IOP. These two models will be used to further understand the role(s) of TGFß1 in glaucoma.

Keywords: intraocular pressure • gene transfer/gene therapy • cytokines/chemokines 
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