Abstract
Purpose :
Inhibitor of differentiation 3 (Id3) gene acts a molecular switch and controls cellular proliferation and differentiation. Recently, we found remarkable corneal fibrosis abrogation in rabbit eyes in vivo by AAV-Id3 gene therapy. This study evaluated the long-term tolerability and safety of AAV5-Id3 gene therapy for eye diseases in vivo using rabbits for 6 months.
Methods :
Eighteen New Zealand White Rabbits were divided into 3 groups. Only one eye of each animal was used. Group-1 received no treatment (Naïve; n=6), Group-2 received AAV5-naked (n=6), and Group-3 received AAV5-Id3 (n=6). AAV5-naked and AAV5-Id3 vector in rabbit eye was administered topically using our published method. Frequent clinical eye exams with slit-lamp, specular and confocal microscopes, ophthalmic coherence tomography, pachymetry, tonometry, Schirmer and fluorescein eye tests in live rabbits and histology in corneas collected after 6 months evaluated tolerability and safety of Id3 gene therapy.
Results :
Time-dependent clinical eye examinations, modified Hackett–McDonald ocular scoring, and multimodal eye imaging showed no signs of ocular toxicity in AAV5-Id3 (Group-3) or AAV5-naked (Group-2) compared to naïve (Group-1) eyes (P > 0.05) for 6 months. Also, AAV5-Id3 and AAV5-naked vector given eyes showed no noticeable changes in corneal thickness, tear flow, intraocular pressure, corneal epithelium and endothelium compared to naïve eyes. Furthermore, AAV5-Id3 and AAV5-naked vector delivered eyes showed no abnormal ocular discharge, blepharospasm, chemosis, or watery eyes. The histological studies found no differences in the naïve, AAV5-naked, and AAV5-Id3 groups (P > 0.05).
Conclusions :
Localized and tissue-targeted AAV5-Id3 gene delivery into corneal stroma is safe and non-toxic to the rabbit eye in vivo.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.