Retinal Neurobiology
Professor Mark W. Hankins
Research in my group explores the neurobiology of the vertebrate retina at the cellular level. This has focused upon the mammalian retina, in particular examining the mechanisms that regulate the complex physiological changes manifested in the shift from day (cone) to night (rod) vision. The functional burden of a mixed (rod/cone) retina are the associated complexities of the diurnal modification to the neural network, much of which involves predictive and long-term modifications to physiology. These are vital adaptations in the primary visual pathway, yet the mechanism and regulation of these circadian/diurnal changes in retinal function remain to be fully explored.
Vertebrate Retina – Historic view of the cellular organisation
We have shown for the first time that the human primary visual cone pathway is regulated by the activities of an irradiance detector that utilizes a novel photopigment (Hankins and Lucas, 2001). The characteristic spectral sensitivity of this pigment raises the interesting possibility that it is conserved in a number of species and sub-serves a broad range of non-image forming light responses. Our work has shown that in addition to providing an independent light input to the circadian system and other recipient brain areas, novel photopigments play a critical role in the regulation of local retinal physiology.
We are currently examining the cell biology of inner-retinal photoreception. The work examines the physiological properties of a novel photoreceptive system in the inner retina that requires neither rods nor cones to function. Our approach has been to develop an imaging system that would allow us to load fluorescent calcium indicator into the ganglion cells of the adult retina and to observe the response to light stimulation over a wide area of the inner retina.
Calcium imaging of light sensitive ganglion cells in the isolated rd/rd cl retina. The sequential series of images (1-11) shows that illumination induced a significant increase in fluorescence of the Ca2+ sensitive indicator (FURA 2). The last panel in the sequence shows successive transient waves in Ca2+ in response to the light stimulus.
We used this approach to provide the first global view of inner retinal photoreception in mammals through an examination of the rodless/coneless (rd/rd cl) retina. We revealed that a remarkable 3% of retinal ganglion cells respond to light in the absence of all classical photoreceptors (Sekaran et al, 2003). We are now extending this work in an attempt to explore the functional relationship between inner retinal photoreceptors and the activity of rod/cone pathways. A proportion of the retinal ganglion cells that respond to light express the candidate photopigment melanopsin. Indeed, ablation of the melanopsin gene in combination with silencing the rods and cones, results in the loss of all accessory visual sensitivity (Hattar et al, 2003).
The imaging approach has also proved invaluable to look at the emergence and development of the non-rod/cone light sensing pathway. Our work on the profiling of opsin expression in the retina has established that melanopsin expression occurs in the embryonic mouse at around E10, much earlier than the classical opsin photopigments. Correspondingly our recent physiological experiments have shown that melanopsin expressing retinal ganglion cells are able to respond to light from the day of birth, thus the retina has this light detecting system in place long before the emergence of rod and cone mediated light signaling.
Representation of Retinal Model of the Human Fovea
In collaboration with Professor Chris Kennard and the newly formed Institute for Biomedical Engineering (Imperial College) we are involved in a number of retina and vision projects that include a cell based mathematical model of the human fovea, reverse engineering the human visual pathway and the Imperial College retinal prosthetic program.
Recent Selected Publications:
Melyan Z; Tarttelin EE; Bellingham J; Lucas RJ; Hankins MW; (17/02/2005) "Addition of human melanopsin renders mammalian cells photoresponsive." Nature volume 433 issue 7027 pp. 741-5 (issn: 1476-4687)
and further information on this topic can be found HERE
Hankins MW. Functional dopamine deficits in the senile rat retina. Visual Neuroscience 17: 839-845., 2000.
Jenkins A and Hankins MW. Long-term light history modulates the light response kinetics of luminosity (L)-type horizontal cells in the roach retina. Brain Res 887: 230-237., 2000.
Hankins MW, Jones SR, Jenkins A, and Morland AB. Diurnal daylight phase affects the temporal properties of both the b- wave and d-wave of the human electroretinogram. Brain Res 889: 339-343., 2001.
Hankins MW and Lucas RJ. The primary visual pathway in Humans is regulated according to long-term light exposure through the action of a nonclassical photopigment. Current Biology 12: 191-198, 2002.
Foster RG and Hankins MW. Non-rod, non-cone photoreception in the vertebrates. Prog Retin Eye Res 21: 507-527, 2002.
Hattar S, Lucas RJ, Mrosovsky N, Thompson S, Douglas RH, Hankins MW, Lem J, Biel M, Hofmann F, Foster RG, and Yau KW. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424: 75-81, 2003.
Jenkins A, Munoz M, Tarttelin EE, Bellingham J, Foster RG, and Hankins MW. VA opsin, melanopsin, and an inherent light response within retinal interneurons. Current Biology 13: 1269-1278, 2003.
Sekaran S, Foster RG, Lucas RJ, and Hankins MW. Calcium imaging reveals a network of intrinsically light-sensitive inner-retinal neurons. Current Biology 13: 1290-1298, 2003.
Tarttelin EE, Bellingham J, Bibb LC, Foster RG, Hankins MW, Gregory-Evans K, Gregory-Evans CY, Wells DJ, and Lucas RJ. Expression of opsin genes early in ocular development of humans and mice. Exp Eye Res 76: 393-396, 2003.
Tarttelin EE, Bellingham J, Hankins MW, Foster RG, and Lucas RJ. Neuropsin (OPN5): a novel opsin identified in mammalian neural tissue. FEBS letters 27818: 1-7, 2003.
Foster RG and Hankins MW. In the Happy Realms of Light. Biologist 51: 135-140, 2004.
Research Funding: Our current work is supported by grants from the Wellcome Trust and BBSRC.
Research Collaborators (Imperial)
Professor Russell G. Foster (Department of Visual Neuroscience)
Professor C. Kennard (Department of Visual Neuroscience)
Dr A. Bharath
Key Research Collaborations External:
Dr Rob J. Lucas (University of Manchester)
Current Members of Lab:
Dr S. Sekaran (s.sekaran@imperial.ac.uk)
Dr Z. Melyan (z.melyan@imperial.ac.uk)
Academic Visitors
Dr H. Momiji (H.momiji@imperial.ac.uk)
Dr G. Lall (School of Biological Sciences, Manchester)
PhD Students:
Ms. S. Jones.
Mr A. Barnard (Manchester)
