Visual Activity Evoked by Infrared in Humans After Dark Adaptation

BACKGROUND: Visual impairment affects 285 million people worldwide. The prevalence of visual impairment in the US is expected to rise from 3.3 million in 2000 to 5.5 million in 2020. This will exacerbate the current economic burden of vision loss, which is already $38.2 billion per year in direct and indirect costs. The leading cause of blindness in high-income countries is due to age-related macular degeneration (AMD), a disease that leads to gradual loss of the photoreceptor cell layer. An estimated 1.75 million people have AMD in the US and another 7.3 million are at risk. Importantly, despite the loss of photoreceptor cells in AMD, the other cellular layers in the retina remain largely intact.

The retina lines the back of the eye and is composed of structural layers. The outer nuclear layer contains photoreceptors called rods and cones. The inner nuclear layer includes bipolar, horizontal, and amacrine cells. Most anteriorly, the ganglion cell layer has axons that exit the eye as the optic nerve. Visual image formation begins when a photon of light enters the eye, passes through all retinal layers, and is absorbed by the photoreceptor cells. These cells transduce the photon of light into an electrochemical signal, which is communicated to bipolar cells, followed by the ganglion cells. Here, an action potential is generated and propagated via the optic nerve to the area of the brain where vision perception occurs. When the eye is dark-adapted, the cells in this pathway are potentially more sensitive to other types of stimuli, such as IR. The investigators believe cation channels called TRP channels in ganglion cells are activated by IR in this dark-adapted state, creating the visual response to IR. Heat is a known activator of certain subtypes of these channels elsewhere in the body. TRP channels are also responsible for IR vision in pit vipers and vampire bats.

Palczewska et al. reported that visual perception to IR occurred through a process of direct two-photon isomerization of visual pigments. However, other evidence suggests IR perception can occur through single IR photon absorption. Studies that use IR to test the functionality of implanted visual prosthesis have noted a greater response to IR in the non-implanted eye when compared to the implanted eye on both VEP tests and ERG. On ERG, a specialized response specific to IR was found called the scotopic threshold response (STR). This response occurs under dark-adapted conditions and correlates with a response at the ganglion cell layer. Direct IR activation of TRP channels on ganglion cells could initiate a visual response. Based on these findings, the investigators hypothesize the human response to IR under dark adaptation occurs at the level of the ganglion cells through heat-activated TRP channels.

RESEARCH DESIGN AIM1: To determine the optimal IR wavelength for human visual perception while dark-adapted in the healthy human eye.

Introduction for Aim 1: The objective of this aim is to determine the optimal wavelength of IR to which the human eye is sensitive. To obtain this objective, the investigators will test the working hypothesis that the healthy human eye, and those with colorblindness, will detect a range of IR wavelengths, with a preference for a specific wavelength. The investigators will test the working hypothesis using a broad-spectrum light source with wavelength-specific bandpass filters in the IR range. The investigators' rationale for this aim is that understanding the optimal IR wavelength of the human eye will aid in future investigations when testing the visual response to IR using diagnostic equipment. This is important because it could impact the way other ophthalmologic modalities use IR to diagnose and treat visual pathologies.

Research Design for Aim 1: A total of healthy 21 participants (15 with normal vision and 6 with colorblindness) aged 18 and older will be recruited using the University of New Mexico (UNM) Clinical and Translational Science Center (CTSC) Clinical Research Volunteer Registry HRRC-06412. Informed consent, participant demographics, past medial and visual history, and a general eye exam will be obtained using the CTSC research coordinator. Each participant will be placed in a dark room for an hour to allow for optimal dark adaptation of the eye. The investigators will use a broad-spectrum light source with wavelength-specific bandpass filters of different IR wavelengths. A total of 12 filters will be used ranging from 850 nm to 1400nm. Intensity curves will be built for each wavelength, by slowly turning up the power until the participant indicates a visual response to the stimulus.

Data Analysis for Aim 1: Data will be analyzed by the investigators. Descriptive statistics will be used to evaluate demographics, general and visual health information, and reported optimal wavelengths. The investigators' analysis will compare differences among responses for each wavelength. To the investigators' knowledge, there have been no studies evaluating which IR wavelength is optimal for human visual perception, thus the investigators assume a low effect size of 10%, which would produce an 82% chance of at least two out of 30 healthy participants giving a preferred response to a specific wavelength. The investigators will describe the estimated effect sizes in response to the findings.

Expected Outcomes for Aim 1: The investigators expect the human eye to perceive a range of IR wavelengths, but have a specific wavelength optimal in terms of brightness.

Potential Problems \& Alternative Strategies for Aim 1: To prevent sampling bias, the investigators plan to obtain a representative sample from New Mexico; however, participants may be younger and more educated than the general population. The confounding bias of light pollution may occur, which would prevent dark adaptation and decrease the IR sensitivity. A photometer will assess the room for background photons.