Maintaining ocular safety with light exposure, focusing on devices for optogenetic stimulation

Abstract

Optogenetics methods are rapidly being developed as therapeutic tools for treating neurological diseases, in particular, retinal degenerative diseases. A critical component of the development is testing the safety of the light stimulation used to activate the optogenetic proteins. While the stimulation needs to be sufficient to produce neural responses in the targeted retinal cell class, it also needs to be below photochemical and photothermal limits known to cause ocular damage. The maximal permissible exposure is determined by a variety of factors, including wavelength, exposure duration, visual angle, pupil size, pulse width, pulse pattern, and repetition frequency. In this paper, we develop utilities to systematically and efficiently assess the contributions of these parameters in relation to the limits, following directly from the 2014 American National Standards Institute (ANSI). We also provide an array of stimulus protocols that fall within the bounds of both safety and effectiveness. Additional verification of safety is provided with a case study in rats using one of these protocols.

Optogenetic therapy: High spatiotemporal resolution and pattern recognition compatible with vision restoration in non-human primates

“…We observed that averaged and normalized photocurrent followed a similar photo-sensitivity curve (Fig. 4D), 18 with activation threshold in the 10 15 photons.cm -2 .s -1 intensity range, and robust responses to light stimuli at a wavelength of 600 nm (+/-10 nm) well below the illumination radiation safety limits for the human eye 21,29,30 . When comparing peak photocurrent or peak firing rate for maximal light intensity (3.15 x 10 17 photons.cm -2 .s -1 ), we found no statically significant difference between the two expression durations ( Fig.…”

“…This was tested under a RGC specific promoter 20 . However, the 5 required blue light intensities were close to radiation safety limits 21 . It was thus clinically important to evaluate other potentials opsins conferring a balance between light sensitivity and channel kinetics 22 .…”

“…The international commission on non-ionizing radiation protection published limits of ocular exposure for visible and infrared radiaton in 2013 28 these limits could be employed in optogenetic systems 21,30 . For a full-field continuous stimulus applied during 8 hours per 48 hours, the maximal permissive retinal peak irradiance is 1.1 x 10 17 photons.cm -2 .s -1 at 600 nm and 8 x 10 15 photons.cm -2 .s -1 at 505 nm.…”

“…But our strategy will rely on light patterns stimulation extracted from an event camera reducing moving faces and objects to their outlines 50,51 . The scarcity of stimulation will increase the maximal permissive retinal peak irradiance 21 .…”

Developing an Outcome Measure With High Luminance for Optogenetics Treatment of Severe Retinal Degenerations and for Gene Therapy of Cone Diseases

“…First, many of the light-sensitive channels available for optogenetics today are relatively insensitive to ambient light 13 , 14 and thus require additional technology that transforms ambient light from natural scenes to a high-illuminance version to be presented to the retina. 15 – 18 Second, there is a need for an encoding scheme that simulates the natural intraretinal processing in order to make a natural scene intelligible by activation of postreceptoral cells. 10 , 19 Third, eyes with low vision tend to have lost normal oculomotor control 20 – 22 and thus require eye tracking methods to allow presentation of high-luminance encoded patterns to a specific part of the retina reproducibly time after time.…”