Neurobiology

Richard H. Masland, Ph.D.

Charles Anthony Pappas Professor of Neuroscience in the Department of Surgery
Professor of Neurobiology, Harvard Medical School

Lab Website: The Masland HMMI Research Page
Additional Lab Website: The Masland MEEI Lab Page

Work in this laboratory concerns the normal cell biology of the neural retina and its disorders.

We have long been interested in the cell populations and synaptic interrelations of the retina. A number of cell types within the retina were discovered here, and we have been carrying out an attempt at the retina “neurome” – a listing of all of the cells present in the retina. To a first approximation, this project is complete. It reveals the retina as a multiply parallel system containing in excess of 60 cell types, which are organized into more than a dozen parallel informational channels. An important piece of unfinished business is to characterize the array of retinal ganglion cells. It is clear that ganglion cells come in something more than 15 different types, each carrying a different transformation of the visual scene to the brain. We are seeking a complete characterization of the array of ganglion cells present in the mouse. The importance of this problem, being studied with collaborators from mouse genetics and computer vision, is that the ganglion cell types define the fundamental elements from which visual perception is built.

With this background, a more recent concern is with the pathophysiology of ganglion cell degeneration in glaucoma. This work is being done in collaboration with Dr. Tatjana Jakobs, Assistant Professor of Ophthalmology, who has primary responsibility for its management. The questions again focus on the retinal ganglion cells, this time in the context of their degeneration in disease. A particular interest is the relationship between the ganglion cell axons and the astrocytes that ensheath them at their point of exit from the eye. The lab has made or obtained transgenic mouse strains that allow direct visualization and molecular analysis of individual astrocytes during the remodeling that occurs after injury. Central questions are the signals that communicate between the optic axons and the glia, and the functional role – helpful or hurtful – of the glial reactivity that occurs after injury.

The lab is also interested in the optogenetic treatment of retinal photoreceptor degenerations. We have demonstrated proof of the principle that rendering the surviving retinal neurons sensitive to light by ectopic expression of a light sensitive protein could restore vision to animals blind from an inherited retinal degeneration. This was done using melanopsin as the light-sensitive protein and viral transduction of retinal ganglion cells; ectopic expression of melanopsin in a large number of ganglion cells restored simple visual abilities to mice blind from an inherited degeneration. Present works seeks to optimize the visual replacement strategy, and to learn how to apply it in primates.