Purpose
Tissue-targeted localized
BMP7
+
HGF
genes delivered into the stroma via nanoparticle effectively treats corneal fibrosis and rehabilitates transparency
in vivo
without acute toxicity. This study evaluated the long-term safety and tolerability of
BMP7
+
HGF
nanomedicine for the eye
in vivo
.
Methods
One eye each of 36 rabbits received balanced salt solution (group 1, naïve;
n
= 12), naked vector with polyethylenimine-conjugated gold nanoparticles (PEI2-GNP; group 2, naked-vector;
n
= 12), or
BMP7
+
HGF
genes with PEI2-GNP (group 3,
BMP7
+
HGF
;
n
= 12) via a topical delivery technique. Safety and tolerability measurements were performed by clinical biomicroscopy in live rabbits at predetermined time intervals up to 7 months. Corneal tissues were collected at 2 months and 7 months after treatment and subjected to histology, immunofluorescence, and quantitative real-time PCR analyses.
Results
Clinical ophthalmic examinations and modified MacDonald–Shadduck scores showed no significant changes in corneal thickness (
P
= 0.3389), tear flow (
P
= 0.2121), intraocular pressure (
P
= 0.9958), epithelial abrasion, or ocular abnormality. Slit-lamp, stereo, confocal, and specular biomicroscopy showed no signs of blepharospasm chemosis, erythema, epiphora, abnormal ocular discharge, or changes in epithelium, stroma, and endothelium after
BMP7+HGF
therapy for up to 7 months, as compared with control groups. Throughout the 7-month period, no significant changes were recorded in endothelial density (
P
= 0.9581). Histological and molecular data were well corroborated with the subjective clinical analyses and showed no differences in the naïve, naked-vector, and
BMP7+HGF
groups.
Conclusions
Localized
BMP7+HGF
therapy is a safe, tolerable, and innovative modality for the treatment of corneal fibrosis.
Translational Relevance
Nanoparticle-mediated
BMP7+HGF
combination gene therapy has the potential to treat corneal fibrosis
in vivo
without short- or long-term toxicity.