Purchase this article with an account.
Yolanda Diebold, Laura Contreras-Ruiz, Giovanni K. Zorzi, Antonio López-García, Karyn F. Siemasko, Denis Hileeto, Margarita Calonge, Michael E. Stern, Begoña Seijo, Alejandro Sánchez; Cationized Gelatine based-Nanoparticles Loaded with Modified MUC5AC Encoding Plasmid for the Treatment of Murine Experimental Dry Eye (EDE). Invest. Ophthalmol. Vis. Sci. 2011;52(14):419.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To achieve an efficient in vivo transfection of MUC5AC, in order to restore its levels in an inflamed ocular surface, improving the physiological parameters associated with this condition.
Cationized gelatin and chrondroitin sulfate-based nanoparticles (NPs) were prepared by ionotropic gelation and loaded with a plasmid coding for a modified MUC5AC protein (pMUC5AC) (P201031678). EDE was induced in C57BL/6 mice with subcutaneous scopolamine and exposure to an air draft for 10 days. 5µl of naked plasmid, blank NPs, pMUC5AC-NPs or cyclosporine A (CsA) were instilled in both eyes 4 times/day for 5 days. Control animals received no instillations. Clinical signs, corneal fluorescein staining and tear production were evaluated before and after EDE induction, and after treatment. MUC5AC expression was evaluated by real time RT-PCR. Ocular structures were processed for pathology evaluation, including goblet cell (GC) count. Two-way ANOVA was done for statistical analysis.
Expression of modified MUC5AC was significantly higher in cornea and conjunctiva of pMUC5AC-NP-treated EDE animals than that of controls. Neither ocular discomfort nor irritation was observed in vivo after NP treatment. Desiccating stress significantly increased corneal fluorescein staining and decreased tear production and GC numbers. However, corneal fluorescein staining and tear production significantly improved after pMUC5AC-NP and CsA treatment. Anterior eye segment of treated mice showed normal architecture and morphology with lack of inflammatory changes.
pMUC5AC-NPs were able to induce the expression of modified MUC5AC in ocular surface tissues, to improve the integrity of corneal epithelial barrier and to increase tear production and GC numbers in dry eye mice. Thus, pMUC5AC-NPs may be a potential therapy for dry eye syndrome.
This PDF is available to Subscribers Only