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Rajiv R Mohan, Suneel Gupta, Nishant Rajiv Sinha, Lynn Martin, Nathan Hesemann, Sabeeh Kamil, Prashant R. Sinha, Praveen Balne, Ratnakar Tripathi, Shyam S Chaurasia; Long-term tolerability profiling of BMP7+HGF overexpression on rabbit cornea in vivo. Invest. Ophthalmol. Vis. Sci. 2021;62(8):928.
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© ARVO (1962-2015); The Authors (2016-present)
Recently, we found targeted BMP7+HGF dual gene therapy applied to stroma via PEI2-GNP effectively treated preformed corneal scar and restored transparency in vivo in rabbit with minimal acute toxicity (Invest Ophthalmol Vis Sci. 2018;59:1045-57). The goal of this study was to evaluate long-term in vivo tolerability of this BMP7+HGF therapy using a rabbit model.
Eighteen New Zealand White rabbits were used and divided into three groups. One eye of rabbit received BSS (n=6), naked-vector (n=6) or BMP7+HGF genes (n=6) via PEI2-GNP nanoparticles using published method (Invest Ophthalmol Vis Sci. 2018;59:1045-57). Rabbits were treated following ARVO guidelines under approved ACUC protocol. Clinical eye exams and diagnostic tools (Slit lamp, HRT3-RCM, Spectralis, and Specular microscopes; and pachymetry, tonometry, Schirmer, fluorescein and MacDonald-Shadduck tests) were employed in live rabbits in a time-dependent manner for 7 months for safety profiling. Thereafter, rabbits were humanely euthanized, corneal tissues were collected, and used for histological, immunofluorescence, and qRT-PCR analyses.
Clinical eye exams detected no signs of chemosis, erythema, blepharospasm, or epiphora in all 3 groups until 7-month. HRT3-RCM, Spectralis and Specular biomicroscopy noted healthy corneal epithelium, stroma, and endothelium; and normal stromal and endothelial cell counts in all groups. No significant changes in intraocular pressure and MacDonald-Shadduck parameters in BMP7+HGF-delivered versus control eyes were observed(p=0.9989, p=0.9876). Histology and molecular investigations revealed no significant differences in cellular phonotype and levels of tested proinflammatory and fibrotic markers in BMP7+HGF-delivered versus control eyes (p=0.9992,p=0.9619; p=0.9646 p=0.98379).
Nanoparticle-mediated BMP7+HGF nanomedicine modality appears tolerable to the eye long-term in vivo.
This is a 2021 ARVO Annual Meeting abstract.
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