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Herpes simplex virus-mediated gene delivery to the rodent visual system
B Spencer1, S Agarwala, M Miskulin
1Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, USA.
Investigative Ophthalmology & Visual Science
|May 8, 2000
Summary
Herpes simplex virus-1 (HSV-1) vectors efficiently deliver genes to mouse and rat visual systems, including retinal pigment epithelium and visual cortex neurons, without causing inflammation.
Area of Science:
- Ophthalmology
- Neuroscience
- Gene Therapy
Background:
- Gene delivery to the visual system is crucial for treating ocular and neurological disorders.
- Herpes simplex virus-1 (HSV-1) vectors offer potential for efficient transgene delivery due to their neurotropic nature.
Purpose of the Study:
- To evaluate the cell types in the mouse and rat visual system capable of expressing a transgene delivered by an attenuated replication-competent HSV-1 vector.
- To assess the efficacy of different delivery routes for HSV-1 vector-mediated gene transfer.
Main Methods:
- Mice and rats were infected with an HSV-1 vector (hrR3) expressing the lacZ gene via topical ocular, intravitreal, intracameral, or visual cortex injection.
- Tissues were collected at specified times and examined for lacZ expression using histochemical staining.
Main Results:
- Topical delivery resulted in transgene expression in corneal and retinal pigment epithelium (RPE) cells.
- Intravitreal injection led to high expression in RPE cells, ciliary body, and optic nerve; retinal ganglion cells were also labeled in rats.
- Intracameral and visual cortex injections effectively targeted various ocular cells and visual cortex neurons, respectively, with no observed pathology.
Conclusions:
- The hrR3 HSV-1 vector successfully delivers functional genes to diverse cell types within the eye and central visual pathways.
- Retrograde transport of the vector to projecting nuclei was observed, indicating its potential for targeting neural circuits.