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A. M. Demetriades, H. Liu, P. L. Gehlbach, T. Deering, L. L. Wei, P. A. Campochiaro; Periocular Delivery of Transforming Growth Factor Beta-1 Inhibits Developmental Eye Growth in Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3843.
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To determine the effect of periocular delivery of transforming growth factor beta-1 (TGFß-1) via adenoviral-mediated expression or recombinant protein delivery on developmental eye growth in mice.
In the recombinant protein delivery group, neonatal C57/BL6J mice (n=10) received daily periocular injections of 3µl of 0.1µg recombinant human TGFß-1 (R&D systems, Minnesota, MN) in the right eye and 3µl of sterile 4mM HCL containing 1mg/ml bovine serum albumin in the left eye from postnatal day (P) 10 to P16. In the adenoviral-mediated expression group, neonatal C57/BL6J mice (n=19) were exposed to 75% oxygen between P7 and P12. On P10 they received a 3µl periocular injection of 3x109 viral particles of an E1- and E3-deleted type 5 adenoviral vector with a CMV promoter expressing active human TGFß-1 (AdTGFß-1) in the right eye and the same concentration/volume of a corresponding null vector (AdNull) in the left eye. All mice were sacrificed on P17 and eyes were rapidly removed and weighed on an electronic analytical balance (Mettler Toledo, Columbus, OH).
Following daily periocular injections of human TGFß-1, there was a statistically significant reduction in eye weight (µg) compared to placebo (11.55 vs. 12.41; n=10; p=0.001). In addition, there was no significant difference between placebo injected control and uninjected eyes (12.42 vs. 12.37; n=6; p=0.829). Following oxygen-induced ischemic retinopathy, there was a statistically significant reduction in eye weight in eyes that received a periocular injection of 3x109 AdTGFß-1 compared to eyes that received a periocular injection of 3x109 AdNull (8.20 vs.10.60; n=19; p<0.001).
Periocular delivery of TGFß-1 via adenoviral-mediated expression or daily recombinant protein injections over a one-week period inhibits murine developmental eye growth. These findings support the role of TGFß-1 in eye growth and development.
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