EIAV vector-mediated delivery of endostatin or angiostatin inhibits angiogenesis and vascular hyperpermeability in experimental CNV

Balaggan, Kamaljit S.; Binley, Katie; Esapa, Margaret; MacLaren, Robert E.; Iqball, Sharifah; Durán, Yanaí; Pearson, R. A.; Kan, On; Barker, Susie E.; Smith, Andrew J.H.; Bainbridge, James; Naylor, Stuart; Ali, Robin R.

doi:10.1038/sj.gt.3302769

Cited by 55 publications

(54 citation statements)

References 44 publications

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“…EIAV vectors delivering sFlt-1, angiostatin or endostatin resulted in 50-60% reduction in the anatomical extent of laser-induced CNV and 20-60% reduction in associated-vascular hyper-permeability compared with control vector groups (Balaggan et al, 60 and unpublished data). More recently, co-delivery of angiostatin and endostatin by EIAV vectors carrying either CMV or VMD2 promoters significantly inhibited CNV, with a trend suggesting greater efficacy than endostatin delivery alone.…”

Section: Posterior Segment Applicationsmentioning

confidence: 99%

Ocular gene delivery using lentiviral vectors

Balaggan

Ali²

2011

Gene Ther

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Substantial advances in our understanding of lentivirus lifecycles and their various constituent proteins have permitted the bioengineering of lentiviral vectors now considered safe enough for clinical trials for both lethal and non-lethal diseases. They possess distinct properties that make them particularly suitable for gene delivery in ophthalmic diseases, including high expression, consistent targeting of various post-mitotic ocular cells in vivo and a paucity of associated intraocular inflammation, all contributing to their ability to mediate efficient and stable intraocular gene transfer. In this review, the intraocular tropisms and therapeutic applications of both primate and non-primate lentiviral vectors, and how the unique features of the eye influence these, are discussed. The feasibility of therapeutic targeting using these vectors in animal models of both anterior and posterior ophthalmic disorders has been established, and has, in combination with substantial progress in enhancing lentiviral vector bio-safety over the past two decades, paved the way for the first human ophthalmic clinical trials using lentivirus-based gene transfer vectors.

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Section: Posterior Segment Applicationsmentioning

confidence: 99%

Ocular gene delivery using lentiviral vectors

Balaggan

Ali²

2011

Gene Ther

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“…Inhibition of vessel growth by endostatin would have required an early and substantial presence of endostatin. 53 54 Endostatin inhibits experimental CNV, [55][56][57] and its expression can be upregulated by orally administered drugs. regulation or exogeneous delivery of endostatin early after PDT might therefore be a useful strategy to increase the efficacy of PDT.…”

Section: Discussionmentioning

confidence: 99%

Effect of verteporfin photodynamic therapy on endostatin and angiogenesis in human choroidal neovascular membranes

Tatar

Shinoda

Adam

et al. 2007

British Journal of Ophthalmology

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Aim: To evaluate the effect of verteporfin photodynamic therapy (PDT) on endostatin with regard to expression of vascular endothelial growth factor (VEGF) in human choroidal neovascular membranes (CNVs) secondary to age-related macular degeneration. Methods: A retrospective review of an interventional case series of 68 patients who underwent removal of CNV. 29 patients were treated with PDT 3-655 days before surgery. 39 CNVs without previous treatment were used as controls. CNVs were stained for CD34, CD105, Ki-67, cytokeratin 18, endostatin, E-selectin and VEGF. ''Predominance score of VEGF over endostatin'' (mean) was defined as the difference between VEGF and endostatin staining scores. Results: In four CNVs treated by PDT 3 days previously, PS was significantly higher in the retinal pigment epithelium (mean = 2.5, p = 0.006) and stroma (mean = 2, p = 0.015) than in the control group (mean = 0). At longer post-PDT intervals, PS was significantly decreased in the retinal pigment epithelium (mean = 0, p = 0.019) and stroma (mean = 0, p = 0.015). Proliferative activity was high (p = 0.023), but mostly related to inflammatory cells. PDT did not influence E-selectin expression significantly. Conclusions: VEGF predominance over endostatin early after PDT might contribute to enhanced angiogenic activity associated with recurrences. Strategies upregulating or replacing endostatin early after PDT might increase the effectiveness of PDT. N eovascular age-related macular degeneration (AMD) is the leading cause of visual loss among elderly in the western world.

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“…[1][2][3][4][5] EIAV based LVs are being developed for a number of different gene therapy applications for a variety of diseases. [6][7][8][9][10][11][12][13] Recent focus has been on the development of ProSavin, which is an EIAV-based LV for the treatment of Parkinson's disease encoding three enzymes required for the dopamine synthesis. 6 Currently, ProSavin is in phase I/II clinical trials that require relatively small amounts of vector material.…”

Section: Introductionmentioning

confidence: 99%