Clint Makino, Ph.D.
Associate Professor of Ophthalmology (Neuroscience)

Massachusetts Eye & Ear Infirmary
Howe Laboratory
243 Charles Street
Boston, MA 02114
Tel.: (617)573-4462
Fax: (617) 573-4290

Vision begins with the absorption of a photon by a visual pigment molecule. This triggers a complex, biochemical cascade that hyperpolarizes the photoreceptor. We are investigating three aspects of these early events of vision. The kinetics of the response affect our absolute sensitivity as well as the rapidity with which we can see. Using transgenic mice, we have determined that the speed of the photoresponse is limited by the rates with which key molecules collide with each other. This work advances our basic understanding of how certain classes of biochemical reactions take place in living cells. It also has important implications for prospective genetic therapies aimed at deleting or replacing defective proteins that produce disease in rods.

         Rod and cone photoreceptors divide the intensity range of vision. Rods are more sensitive, but cones operate over a wider dynamic range and provide the basis for color vision. Rod and cones are thought to utilize different visual pigments, specialized for their individual needs. We discovered an exception to the rule. A convergence of spectral, immunohistochemical and molecular biological evidence indicated that a rod and a cone from salamander express the same visual pigment. Interestingly, the pigment interacts with different transducin G proteins in the two cell types. This research is being used to define the molecular basis for the functional differences between rods and cones and may help to reveal clues about the evolutionary transformation of cones into rods.   

         Rods attenuate their sensitivity in steady light or light adapt in order to extend their dynamic range. We mapped the time course of light adaptation using electrophysiological methods. Although previous studies have shown light adaptation to be complete within a few seconds, we found an additional, slow phase that evolved over many tens of seconds. The magnitude of each phase was large and combined to desensitize the rod to steady light by several thousand fold. In future studies, we want to elucidate the molecular mechanisms underlying light adaptation. These mechanisms may help us to understand how some retinal diseases produce profound losses in rod sensitivity.

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Howe Home Page      E-Mail: clint_makino@meei.harvard.edu