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Brian Spencer, Seema Agarwala, Michael Miskulin, Morton Smith, Curtis R. Brandt; Herpes Simplex Virus–Mediated Gene Delivery to the Rodent Visual System. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1392-1401.
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purpose. To determine the types of cells in the visual system of the mouse and
rat that can express a transgene delivered by an attenuated replication
competent Herpes simplex virus-1 (HSV-1) vector.
methods. C57/BL6 × BALB/C mice and Albino rats were treated with 1 ×
107 pfu of the HSV-1 ribonucleotide reductase mutant (hrR3)
expressing the Escherichia coli lacZ gene. The hrR3
virus was delivered by topical application to the cornea, intravitreal
(IV) injection, intracameral injection (IC), or stereotactic injection
into the visual cortex (VC). At specified times postinfection, animals
were killed and tissues were removed, fixed, sectioned, and stained
with X-gal or hematoxylin and eosin for histochemical and
results. Topical delivery after corneal scarification in both mouse and rat
resulted in lacZ expression in 25% of the corneal
epithelial cells and 25% of the retinal pigment epithelium (RPE)
cells. Topical application without concurrent scarification also
resulted in transgene delivery to 20% of the RPE cells of the rat but
not the mouse. IV injection resulted in expression primarily in RPE
cells, with up to 100% of the cells expressing lacZ in
the mouse and rat. Other cells expressing the transgene included
ciliary body (CB) and optic nerve cells. Up to 25% of the retinal
ganglion cells in the rat expressed lacZ, but only
rarely in mice. IC delivery in rats resulted in expression in
trabecular meshwork, CB cells, RPE, and iris epithelium. Injection into
area 17 of the rat VC resulted in efficient labeling of the VC neurons
and neurons in the lateral geniculate nucleus without any evident
pathology or inflammation. Neither inflammation nor disease pathology
was observed in either the mouse or rat after any route of delivery.
conclusions. It was demonstrated that the hrR3 HSV-1 virus can deliver a
functioning gene to several cell types in the eye and neurons in the VC
and that the virus can move via retrograde transport to nuclei that
project to the VC.
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