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Eduardo M. Rocha, Paola Perez Riveros, Giovanni Di Pasquale, John A. Chiorini; AAV Vector As A Potential Drug Delivery System In Lacrimal Gland Of Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3721.
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© ARVO (1962-2015); The Authors (2016-present)
Lacrimal gland (LG) deliveries defensive and metabolic factors to the ocular surface. In diseases like Sjögren’s syndrome, LG dysfunction is incurable and jeopardizes vision. The aim of this study is to investigate the use of adeno-associated virus (AAV) as gene vectors for lacrimal gland therapy.
Balb/c male and female 8 weeks old mice were used to investigate AAV gene vector transfer to LG. AAV vectors (AAV 2, AAV 4, AAV 5, AAV 5w8, AAV x5, AAV 9, AAV 12 and BAAV) carrying the firefly luciferase reporter gene were administered in LG by direct injection, and evaluated for its expression by measuring luminescence in vivo (Xenogen IVIS Imaging System), and by immunohistochemistry (IHC). Tissue integrity was evaluated by ocular surface observation, phenol red test (PRT) and histology.
The present work revealed that AAV gene vector was able to transduce mice LG. The AAV serotype with highest transduction activity was AAV9, followed by AAV5w8, AAV5 and AAV2. Transduction could be detected as soon as 24 h post-recombinant virus administration and lasted for at least 30 days, when the study was terminated. Comparison with AAV5w8 between male and female mice did not show difference (P=0.69). Overall LG transduction was confirmed by IHC staining. Ocular exam, PRT and histology were similar to controls.
Gene delivery to LG by AAV is feasible and well tolerated by the animals. Although optimal transduction is serotype dependent, the present work provides support for future research in AAV gene therapy for dry eye syndrome.
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