In vivo laser targeted gene therapy of retina ganglion cells (Conference Presentation)

Ariel Wilson; Javier Mazzaferri; Éric Bergeron; Sergiy Patskovsky; Paule Marcoux-Valiquette; Santiago Costantino; Przemyslaw Sapieha; Michel Meunier

doi:10.1117/12.2509870

13 March 2019 In vivo laser targeted gene therapy of retina ganglion cells (Conference Presentation)

Ariel Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, Michel Meunier

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Proceedings Volume 10858, Ophthalmic Technologies XXIX; 108580W (2019) https://doi.org/10.1117/12.2509870
Event: SPIE BiOS, 2019, San Francisco, California, United States

Abstract

There is a current void in efficient, cell-specific, retinal drug delivery systems, thus developing a safe, effective, selective drug delivery system would open novel therapeutic avenues. We previously demonstrated that femtosecond (fs) laser irradiation can selectively transfect DNA plasmids into cultured cells in the presence of functionalised gold nanoparticles (AuNPs) (1). Here, we sought out to selectively optoporate retinal cells in vivo with functionalized AuNPs and a 800nm fs laser. The cell-surface Kv1.1 voltage-gated channel was chosen to target retinal ganglion cells (RGCs) in the rat retina. The eyes of anesthetized rats were placed in the beam path of an optical system consisting of a fs laser and an ophthalmoscope for fundus visualization. Following Kv1.1-AuNP and FITC-dextran intravitreal injection and incubation, irradiation resulted in FITC uptake by retinal cells. In addition, similar experiments with Cy3-siRNA clearly show that the technique can effectively deliver siRNA into RGCs. Importantly, neither AuNP intravitreal injection nor irradiation resulted in RGC death, as determined by RBPMS quantification 1 week following AuNP injection and/or irradiation. Since living biological tissues absorb energy very weakly at 800nm, this non-invasive tool may provide a safe, cost effective approach to selectively target retinal cells and limit complications associated with surgical interventions, and potential biological hazards associated with viral-based gene therapy. In addition, given the extensive use of lasers in ophthalmic practice, our proposed technology may be seamlessly inserted to current clinical setups. (1) E. Bergeron et al, Nanoscale, 7, 17836 (2015).

Conference Presentation

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Ariel Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, and Michel Meunier "In vivo laser targeted gene therapy of retina ganglion cells (Conference Presentation)", Proc. SPIE 10858, Ophthalmic Technologies XXIX, 108580W (13 March 2019); https://doi.org/10.1117/12.2509870

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KEYWORDS

Laser therapeutics

Retina

Femtosecond phenomena

Gold

Laser applications

Laser irradiation

Nanoparticles

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