The contribution of inner retinal photoreception to mouse visual function

Lead Research Organisation: University of Manchester
Department Name: Life Sciences


Sight is our most valued sense, and has been a perennial subject of scientific investigation over the centauries. Nonetheless, we continue to find out exciting new things about it. Among the most surprising of these has been that the rod and cone cells in the retina are not our only photoreceptors. In fact, we now know that another group of cells, called mRGCs, are capable of responding directly to light. These mRGCs work fairly well even when rods and cones are absent, and thus provide residual photosensitivity in some blind people. Until now, however, mRGCs have been thought to mainly provide input to crude 'sub conscious' responses to light, such as setting the size of the pupil in our eyes and ensuring that our internal biological clocks are set to local time. There has been little indication that they could also help us to see. We have recently shown that, in fact, signals from mRGCs appear throughout those parts of the brain responsible for visual perception. How then do mRGCs help us to see? Answering that question is the subject of this proposal. We will achieve this by providing visual stimuli capable of selectively activating mRGCs to several lines of transgenic mice. We will then be able to determine whether mice can use these stimuli to navigate a maze, and also what impact they have on the electrical activity of neurons in parts of the brain responsible for vision. Our work has the capacity to provide a new understanding of how we perceive the world. Because mRGCs survive in people with rod and cone degeneration, this information may be particularly pertinent for the blind and partially sighted.

Technical Summary

We have recently shown that, far from being largely segregated from the primary visual pathways as previously thought, signals from mRGC photoreceptors are extraordinarily widespread across the visual thalamus and cortex. This implies a substantial contribution to pattern vision and perception, but at present the nature of this contribution is unknown. Our electrophysiological recordings from the mouse dorsal lateral geniculate nucleus (dLGN) reveal melanopsin signals in the ~40% of neurons showing sustained activation to a light step. It allows this sub-population of neurons to maintain firing under extended light exposure, and to trace the irradiance of a full field light stimulus over at least 6 decimal orders. Our first hypothesis regarding melanopsin's visual functions is therefore that it helps encode levels of ambient light for perceptions of global 'brightness'. We next propose that this system also conveys some spatial information, allowing mRGCs to contribute a spatial map of brightness. As our new data reveals that the melanopsin signal is merged with conventional visual input by the level of the thalamus, a final possibility is that these information streams interact, allowing mRGCs to modulate the activity of rod/cone based visual processes. We propose behavioural and in vivo electrophysiological experiments that, in combination with advanced informatics techniques, will allow us to define mRGC contributions to encoding a wide range of visual stimuli from simple full field illumination to 'natural' visual scenes. We will take advantage of the difference in spectral sensitivity of melanopsin vs rod/cone photoreceptors to selectively evoke melanopsin-based visual responses. Importantly, this approach will allow us to study melanopsin vision in animals with an intact visual system, which is a prerequisite for approaching an accurate and complete view of mRGC influence.

Planned Impact

This project will reveal how the visual system uses melanopsin photoreception. We see two potential practical applications of this knowledge. 1.) Lighting design and electronics industries. At present, artificial lighting and visual display units are designed solely with cone photoreceptors in mind. New lighting technologies (OLED, QD-LED) have the capacity to provide a closer approximation of the spectral and brightness ranges of natural scenes. Our experiments will reveal whether this technology could be utilised to provide information to the melanopsin system, and thus bring the viewer experience closer to that in natural (outdoor) visual environments. Our plan for dissemination of this knowledge will initially be to use our contacts within the lighting industry. This will be achieved by speaking at industry forums organised by the main lighting standards organisations at national (National Physical Laboratory) and international (Committee International de l'Eclairage) levels, and contributing articles to trade publications. Should our discoveries suggest immediate practical applications we will work with UMIP (our University's knowledge and technology transfer organisation) to seek protection for intellectual property, and to identify suitable industrial partners for product testing and development. 2.) New approaches to blindness. Millions around the world suffer varying degrees of blindness thanks to rod/cone degeneration. At present these conditions are largely untreatable. However, we know that melanopsin photoreception survives even complete rod/cone degeneration. Could this explain why complete loss of light perception is so rare in these subjects? If so, could strategies to support mRGC survival and function under these conditions present a simple new option for improving vision? At earlier stages of degeneration does melanopsin help to support vision? If so, could new visual aides designed to optimise melanopsin vision improve sight in these patients? Determining melanopsin's contribution to vision in sighted individuals represents the first step to answering these important questions. Should our findings indicate that the answer to any of them is likely to be 'yes', then we will move forward to parallel animal and clinical studies of melanopsin vision in retinal disease. For this task, we are fortunate to have The Manchester Royal Eye Hospital in an adjoining building. The principle applicant has active collaborations with clinicians in this unit (Profs Paul Bishop and Graeme Black), and will aim to work with them to study melanopsin's contribution to vision in subjects with retinal degeneration and to test potential clinical interventions. This strategy should allow us to realise any clinical benefits arising from our studies within 5-8 years. Training This project represents an excellent opportunity for the researcher coapplicant to obtain training in computational and informatics techniques to complement his current expertise in electrophysiology. This will make him well placed to contribute to the coming era in biology in which higher-level analyses of large datasets will be so important.


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Description We set out to determine the degree to which a newly discovered photoreceptor in the eye (melanopsin) might contribute to our ability to perceive the world around us. We hypothesised that melanopsin might help us to distinguish the brightness of environments and in the course of the grant provided evidence that this was indeed the case in both humans and mice. We further proposed that melanopsin might be used as an independent measure of brightness that was used to define light adaptation. We also showed that this was the case. We finally set out to determine the extent to which melanopsin could be used to distinguish surface brightness. We find that melanopsin can indeed be used to distinguish even relatively small differences in surface brightness, but that it have very poor spatial resolution compared to that provided by rods and cones.
Exploitation Route Our findings suggest simple modifications to visual display and printing technologies that could improve their appearance. We are in the process of turning this insight into a protectable IP strategy.
Sectors Digital/Communication/Information Technologies (including Software),Electronics

Description This work contributed to our development of a new architecture for image capture and display technologies, in which the standard 3 (RGB) subpixels are replaced by a 4 sub pixel design to allow control over colour, brightness and melanopsin activity. We developed a prototype display and obtained ISS funding to visit potential commercial partners in North America (Apple, Chirstie, Dolby) and at the SPIE meeting in San Francisco (LG) in 2019. The technology was well received by these partners, although it was generally considered at too early a stage of development for them to take forward. Christie however are currently developing a full scale prototype for evaluation.
First Year Of Impact 2018
Sector Digital/Communication/Information Technologies (including Software),Electronics
Impact Types Cultural,Economic

Description CIE Joint Technical Committee 9
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guideline committee
Description BBSRC IAA The University of Manchester
Amount £300,000 (GBP)
Funding ID BB/S506692/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 03/2018 
End 03/2021
Description Look200 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I worked with a local artist who produced some paintings based upon our research. These were painted in the reception area of the Manchester Royal Eye Hospital to celebrate its 200th anniversary and are now hung there alongside captions describing their scientific basis. While the artist was painting these pictures she talked to members of the public (patients, passersby etc) about what she was doing and the pictures now sit in the reception area for people to look at and consider while they are waiting for appointments.

A very large number of people have seen the pictures being painted and will now see them on the walls of the hospital. They come with short, easy to understand descriptions of the science underpinning them.
Year(s) Of Engagement Activity 2014
Description SciBar event, Knutsford, Cheshire 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Ran a seminar and discussion on animal photoreception for the Kuntsford branch of SciBar run by the British Science Association

no actual impacts realised to date
Year(s) Of Engagement Activity 2013
Description Trilux Akademie 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Seminar to explain the potential implications of our research for healthy architectural lighting. Presented to an audience of lighting designers and engineers.
Year(s) Of Engagement Activity 2016