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Mark Christian Butler, Jack M Sullivan; Novel Retinal Light Damage Device for Animal Models of Retinal Degeneration and Testing Gene Therapies. Invest. Ophthalmol. Vis. Sci. 2016;57(12):101.
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© 2017 Association for Research in Vision and Ophthalmology.
Retinal light damage is a common approach to testing candidate therapeutic agents for their ability to rescue retinal degenerative diseases. Historical devices still in use (e.g. Noell WK et al., 1966, IOVS 5(5): 450-473) are seriously limited in terms of control of the spectral quality, intensity, and spatial distribution of light. To address these limitations we developed a novel retinal light damage instrument for mice that is a versatile and useful experimental device.
To create a uniform distribution of light we employed an integrating sphere optical model for the light exposure chamber. The core of the device was generated with 3D printer. High intensity die level LED emitter devices (Phillips LumiLEDs) were positioned along the upper and lower rings of the device to achieve a uniform illumination of the sphere. LEDs used provided royal blue (447.5 nm peak), cyan (502 nm peak), green (530 nm peak), and deep red (655 nm peak) colors. Intensities of each color were independently modulated. We called the device Northern Lights. Retinal light damage was assessed by ultrahigh resolution OCT.
The Northern Lights design creates a uniform illumination inside a Ganzfeld sphere for all spectral bands utilized. Light intensity is modulated electronically between 100-4,000 lux. Mice are placed in the Ganzfeld sphere with pupils dilated with atropine. The ocular integrating spheres become conjugate spheres with the Ganzfeld which leads to expected uniform light within the globes. Retinal light damage, which in rodents is initiated with rhodopsin activation (peak absorption 500 nm), is highly sensitive to the cyan (502 nm) stimulus whereas red light has little spectral overlap. C57BL/6J mice showed no retinal degeneration to the cyan stimulus. A double knockout mouse model of Stargardt juvenile macular degeneration and AMD (ABCA4//RDH8) showed extensive retinal damage to cyan but not red light.
We developed a novel retinal light damage device based upon a true Ganzfeld integrating sphere. The device provides the expected performance in inducing outer retinal (photoreceptor) light damage in mutant but not control mouse models. It can be used in quantitative therapeutic rescue strategies (e.g. gene therapy) in animal models of human disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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