Purchase this article with an account.
N. E. Wood, L. Guo, W. Cheung, T. E. Salt, M. F. Cordeiro; Targeting the Optic Nerve Head (ONH) for Modulation of the Mechanical Theory of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3273.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Extracellular matrix (ECM) deposition and a wound healing response at the ONH are believed to be responsible for the compression of retinal ganglion cell (RGC) axons in the mechanical theory of glaucoma. In this study we investigated whether and how ONH cells could be selectively transduced with a viral vector.
An AAV2 viral vector with a GFP reporter (Resverlogix, Canada) was used with 5 different delivery routes of administration (intravitreal (V), retrobulbar (RB), subTenon’s (ST), gelfoam (G), scleral (S)) at 4 different viral loads (0, 0.0033 x1012, 0.0132 x1012 and 0.0264 x1012) in 48 eyes of DA rats under general anaesthetic. Imaging in vivo using a cSLO and a fluorescent setting was carried outat 3, 7 and 21 days after administration with histological analysis thereafter. Assessment of ONH transduction was performed using semi-quantitative grading by individuals (n=5) blinded to the treatment groups.
All routes appeared to achieve some ONH transduction at 3 days, although V, RB and S were associated with high levels of retinal cell transduction. However, at 7 days, there was a significant difference between delivery routes of administration (P<0.05), with the ST route giving the greatest number of GFP positive ONH cells imaged in vivo. The highest dose of AAV2 delivered ST produced the most efficient transduction at 21 days. Although predominantly superficial, histological analysis confirmed GFP expression distributed throughout the multilayered structure of the ONH.
These results show quite clearly that the sub-Tenon mode of delivery of the AAV2 virus was most effective in selectively transducing ONH cells. Furthermore, the highest dose appeared most successful in achieving a sustained level of transduction at 21 days. We believe using this vector it may be possible to modulate ONH cell activity and that this may be a potential approach in the treatment of glaucomatous disease.
This PDF is available to Subscribers Only