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In Vivo Gene Transfer to the Rabbit Common Carotid Artery Endothelium
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Gene transfer to the outflow tract.

Yalong Dang1, Ralitsa Loewen1, Hardik A Parikh2

  • 1Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, USA.

Experimental Eye Research
|May 2, 2016
PubMed
Summary

Gene therapy using viral vectors offers a promising approach to treat open-angle glaucoma by targeting intraocular pressure. Different vector types, including lentiviral and adeno-associated viral vectors, show potential for long-term gene expression to manage glaucoma.

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Area of Science:

  • Ophthalmology
  • Gene Therapy
  • Molecular Biology

Background:

  • Elevated intraocular pressure is the primary driver of open-angle glaucoma, with resistance occurring in the trabecular meshwork and Schlemm's canal.
  • Gene transfer via viral vectors offers efficient mechanisms for therapeutic intervention in ocular diseases.
  • Understanding vector kinetics and long-term expression is crucial for developing effective glaucoma treatments.

Purpose of the Study:

  • To review the application of viral vectors for gene transfer in managing open-angle glaucoma.
  • To compare the characteristics and potential of various viral and nonviral gene transfer methods.
  • To highlight recent advancements and future strategies in gene therapy for glaucoma.

Main Methods:

  • Review of viral vector systems (lentiviral, AAV, adenoviral, herpesviral) and nonviral transfection methods.
Keywords:
Gene therapyGlaucomaIntraocular pressureOutflow tractTrabecular meshwork

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  • Analysis of vector transduction pathways (conventional, uveoscleral) and integration capabilities.
  • Examination of gene transfer of non-coding RNAs (siRNA, miRNA, lncRNA) and their targets (RhoA, prostaglandin, TGF-β, myocilin).

    • Main Results:

    • Viral vectors can transduce cells in the anterior chamber, with varying kinetics across species.
    • Long-term transgene expression is achievable with integrating vectors (e.g., lentiviruses), while non-integrating vectors face degradation.
    • Preclinical studies show promise in targeting specific pathways and modifying outflow tract elements for glaucoma treatment.

    Conclusions:

    • Gene therapy holds significant potential for treating glaucoma, with viral vectors offering diverse options for gene delivery and expression.
    • Careful selection of vector type is essential to balance efficiency, longevity, and safety, considering integration and immunogenicity.
    • Emerging strategies focus on downstream outflow tract modifications and cell-based therapies for enhanced glaucoma management.