Related Experiment Video
Updated: May 3, 2026
08:55
Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
8.9K
Outflow tract ablation using a conditionally cytotoxic feline immunodeficiency viral vector
Ze Zhang1, Amardeep S Dhaliwal, Harry Tseng
1Yale University School of Medicine, New Haven, Connecticut.
Investigative Ophthalmology & Visual Science
|January 23, 2014
Summary
A new vector system enables targeted trabecular meshwork (TM) cell ablation in vivo, lowering intraocular pressure (IOP). TM cellularity and IOP recovered post-ablation, offering a model for studying TM function.
Area of Science:
- Ophthalmology
- Gene Therapy
- Cell Biology
Background:
- The trabecular meshwork (TM) is crucial for regulating intraocular pressure (IOP).
- Developing in vivo models for TM research is essential for understanding ocular physiology and disease.
- Targeted ablation of TM cells can provide insights into IOP regulation and potential therapeutic strategies.
Purpose of the Study:
- To develop an in vivo model for vector-mediated trabecular meshwork (TM) ablation and replacement.
- To investigate the efficacy and safety of a novel vector system for targeted TM cell destruction.
Main Methods:
- A conditionally cytotoxic and trackable vector (HSVtkG) expressing herpes simplex virus 1 thymidine kinase (HSVtk) and enhanced green fluorescent protein (eGFP) was engineered.
- In vitro optimization of ablation using ganciclovir (GCV) was performed. In vivo experiments involved intracamerally injecting rats with HSVtkG or a control vector (GINSIN), followed by systemic GCV administration.
- Outcomes including intraocular pressure (IOP), central corneal thickness (CCT), and TM cellularity were assessed over 8 weeks. Gonioscopy and histology were used to evaluate transduction, ablation, and inflammation.
Main Results:
- In vitro studies established effective ablation parameters, with apoptosis identified as the cell death mechanism.
- In vivo, vector transduction targeted the TM, and GCV administration led to the disappearance of eGFP fluorescence in transduced cells.
- HSVtkG-mediated TM ablation significantly reduced IOP by 25% post-GCV, with subsequent recovery of TM cellularity and IOP. No significant changes in CCT or inflammation were observed.
Conclusions:
- A novel vector-based system for inducible ablation of outflow tract cells was successfully developed.
- Trabecular meshwork ablation effectively lowered IOP, demonstrating the TM's role in pressure regulation.
- This model holds promise for studying TM stem cells, cell migration, and pressure regulation mechanisms in the eye.
