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Luis Fernando Nominato, Ana Carolina Dias, Lara Dias, Eduardo M Rocha; Lacrimal gland gene transfer by recombinant adenovirus encoding human soluble VEGFR1 inhibits neovascularization in cornea alkali burn model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4515.
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© ARVO (1962-2015); The Authors (2016-present)
The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 encoding human VEGF receptor 1 (Ad-VEGFR1) for delivering gene therapy to the lacrimal gland (LG), (2) to investigate whether expression of recombinant soluble VEGFR1 acts in corneal neovascularization induced by alkali burn and (3) to evaluate the safety of those vectors to the target tissues and systemic spreading.
Ad-VERGFR1 viral vectors (25 μl, 1x109 pfu/mL) of were injected in the right LG of Wistar male adult rats and evaluated in parallel with control animal that received Ad-Null vector (25 μl, 1x109 pfu/mL) of or saline (25μl), prior to ipsilateral cornea alkali burn with NaOH 1M. After 7 days the animals were tested for changes in LG by histology and qRT-PCR, tear secretion were measured with phenol red thread, corneal neovascularizantion were observed in the slit lamp and human s-VEGFR1 was quantified in serum by Elisa.
Ad-VEGFR1 successfully transduced the LG, as detected by qRT-PCR. The percentage of neovascularized area within the cornea was reduced in the group treated with Ad-VEGFR1 compared to the treated with Ad-Null and saline. It did not affect the LG histology nor tear secretion and s-VEGFR1 was not detected in serum.
These results not only support that adenoviral vectors was safe for LG structure and function but also demonstrate that using the LG as the target tissue, local expression of s-VEGFR1 might be a feasible approach for inhibiting the development of corneal neovascularization.
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