Optical modulation of transgene expression in retinal pigment epithelium

D. Palanker; D. Lavinsky; T. Chalberg; Y. Mandel; P. Huie; R. Dalal; M. Marmor

doi:10.1117/12.2001923

26 March 2013 Optical modulation of transgene expression in retinal pigment epithelium

D. Palanker, D. Lavinsky, T. Chalberg, Y. Mandel, P. Huie, R. Dalal, M. Marmor

Proceedings Volume 8567, Ophthalmic Technologies XXIII; 85670A (2013) https://doi.org/10.1117/12.2001923
Event: SPIE BiOS, 2013, San Francisco, California, United States

Abstract

Over a million people in US alone are visually impaired due to the neovascular form of age-related macular degeneration (AMD). The current treatment is monthly intravitreal injections of a protein which inhibits Vascular Endothelial Growth Factor, thereby slowing progression of the disease. The immense financial and logistical burden of millions of intravitreal injections signifies an urgent need to develop more long-lasting and cost-effective treatments for this and other retinal diseases. Viral transfection of ocular cells allows creation of a “biofactory” that secretes therapeutic proteins. This technique has been proven successful in non-human primates, and is now being evaluated in clinical trials for wet AMD. However, there is a critical need to down-regulate gene expression in the case of total resolution of retinal condition, or if patient has adverse reaction to the trans-gene products. The site for genetic therapy of AMD and many other retinal diseases is the retinal pigment epithelium (RPE). We developed and tested in pigmented rabbits, an optical method to down-regulate transgene expression in RPE following vector delivery, without retinal damage. Microsecond exposures produced by a rapidly scanning laser vaporize melanosomes and destroy a predetermined fraction of the RPE cells selectively. RPE continuity is restored within days by migration and proliferation of adjacent RPE, but since the transgene is not integrated into the nucleus it is not replicated. Thus, the decrease in transgene expression can be precisely determined by the laser pattern density and further reduced by repeated treatment without affecting retinal structure and function.

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D. Palanker, D. Lavinsky, T. Chalberg, Y. Mandel, P. Huie, R. Dalal, and M. Marmor "Optical modulation of transgene expression in retinal pigment epithelium", Proc. SPIE 8567, Ophthalmic Technologies XXIII, 85670A (26 March 2013); https://doi.org/10.1117/12.2001923

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KEYWORDS

Laser therapeutics

Luminescence

Eye

Green fluorescent protein

Optical coherence tomography

Transmission electron microscopy

Modulation

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