Gene Transfer to Trabecular Meshwork Endothelium via Direct Injection into the Schlemm Canal and In Vivo Toxicity Study

Purpose: Our aim was to investigate the efficiency of adenoviral gene transfer via direct injection into the Schlemm canal ex vivo in human donor eyes and to examine the effect of human MMP-3 transgene expression in a rat model in vivo. Methods: A viscocanalostomy-like operation was performed and adenoviral vector encoding for MMP-3 and green fluorescent protein was injected into human Schlemm canal or rat anterior chamber. Results: Transgene expression was high in trabecular meshwork endothelium in human donor eyes. In vivo, adenovirus caused dose-dependent inflammation. Conclusions: Direct injection of adenoviral vectors into the Schlemm canal has potential in glaucoma treatment.

[1]  B. Pützer,et al.  Adenoviral p53 gene transfer inhibits human Tenon’s capsule fibroblast proliferation , 2005, British Journal of Ophthalmology.

[2]  B. Pützer,et al.  Antitumor capacity of a dominant-negative RET proto-oncogene mutant in a medullary thyroid carcinoma model. , 2003, Human gene therapy.

[3]  P. Kaufman,et al.  Adenovirus-Mediated Gene Therapy Using Human p21WAF-1/Cip-1to Prevent Wound Healing in a Rabbit Model of Glaucoma Filtration Surgery , 2002 .

[4]  E. Tamm.  Myocilin and glaucoma: facts and ideas , 2002, Progress in Retinal and Eye Research.

[5]  M. Civan,et al.  Human trabecular meshwork cell volume regulation. , 2002, American journal of physiology. Cell physiology.

[6]  D. Epstein,et al.  Gene transfer of dominant-negative RhoA increases outflow facility in perfused human anterior segment cultures. , 2002, Molecular vision.

[7]  P. Kaufman,et al.  Adenovirus-mediated gene therapy using human p21WAF-1/Cip-1 to prevent wound healing in a rabbit model of glaucoma filtration surgery. , 2002, Archives of ophthalmology.

[8]  C. Kee,et al.  Stromelysin gene transfer into cultured human trabecular cells and rat trabecular meshwork in vivo. , 2001, Investigative ophthalmology & visual science.

[9]  D. Epstein,et al.  Expression of aquaporin-1 in human trabecular meshwork cells: role in resting cell volume. , 2001, Investigative ophthalmology & visual science.

[10]  T. Stiewe,et al.  Improved safety through tamoxifen-regulated induction of cytotoxic genes delivered by Ad vectors for cancer gene therapy , 2000, Gene Therapy.

[11]  P. Friedl,et al.  Immortalization of human corneal endothelial cells using electroporation protocol optimized for human corneal endothelial and human retinal pigment epithelial cells. , 2000, Acta ophthalmologica Scandinavica.

[12]  D. Epstein,et al.  Genes upregulated in the human trabecular meshwork in response to elevated intraocular pressure. , 2000, Investigative ophthalmology & visual science.

[13]  F. Graham,et al.  Effects of Stuffer DNA on Transgene Expression from Helper-Dependent Adenovirus Vectors , 1999, Journal of Virology.

[14]  D. Epstein,et al.  Adenoviral reporter gene transfer to the human trabecular meshwork does not alter aqueous humor outflow. Relevance for potential gene therapy of glaucoma , 1999, Gene Therapy.

[15]  D. Miller,et al.  Viscocanalostomy for open-angle glaucoma in black African patients. , 1999, Journal of cataract and refractive surgery.

[16]  J. Samples,et al.  Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. , 1998, Investigative ophthalmology & visual science.

[17]  D. Epstein,et al.  Gene transfer to the human trabecular meshwork by anterior segment perfusion. , 1998, Investigative ophthalmology & visual science.

[18]  V. Sheffield,et al.  Clinical features associated with mutations in the chromosome 1 open-angle glaucoma gene (GLC1A) , 1998, The New England journal of medicine.

[19]  J. Crowston,et al.  Long term growth arrest of human Tenon’s fibroblasts following single applications of β radiation , 1998, The British journal of ophthalmology.

[20]  E. Tamm,et al.  Ocular adenovirus gene transfer varies in efficiency and inflammatory response. , 1996, Investigative ophthalmology & visual science.

[21]  J. Morrison,et al.  Circadian rhythm of intraocular pressure in the rat. , 1996, Current eye research.

[22]  J. Rohen,et al.  Quantitative analysis of 'plaque material' in the inner- and outer wall of Schlemm's canal in normal- and glaucomatous eyes. , 1986, Experimental eye research.

[23]  E. Zypen.  Experimental Morphological Study on Structure and Function of the Filtration Angle of the Rat Eye , 1977 .

[24]  E. van der Zypen.  Experimental morphological study on structure and function of the filtration angel of the rat eye. , 1977, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde.