Our research focuses on basic mechanisms of visual information processing by the retina and particularly on how rod and cone photoreceptors transmit their visual information to downstream horizontal and bipolar nerve cells. Rods and cones are different from many other nerve cells in that they do not produce sodium-dependent action potentials but instead respond to light with graded changes in membrane potential. These light-evoked voltage changes modulate calcium influx through dihydropyridine-sensitive calcium channels that in turn control release of the neurotransmitter, glutamate, from photoreceptor terminals. Over-stimulation of calcium channels and glutamate receptors can promote nerve cell damage in a number of eye disease including glaucoma, stroke, ischemia, and perhaps macular degeneration. Thus, in addition to providing critical insights into the mechanisms of vision, studies on the regulation of synaptic transmitter release from photoreceptors may further development of more effective neuroprotective strategies. Our current research includes studies on the calcium dependence of glutamate release from photoreceptors and on the modulation of photoreceptor calcium channels by neurotransmitters (e.g., dopamine and adenosine) and, less conventionally, by chloride ions.
To study neurotransmission in the retina, we employ a variety of approaches including patch clamp recording techniques (single channel, perforated patch whole cell, ruptured patch whole cell) and dynamic imaging with intracellular indicator dyes (e.g., chloride-sensitive dyes such as MEQ and calcium-sensitive dyes such as Fluo-4 and Fura-2). To measure exocytosis from rod and cone terminals, we use capacitance measurement techniques, flash photolysis of caged calcium compounds, and simultaneous paired whole cell recordings (e.g., rod-horizontal cell or cone-bipolar cell pairs) from photoreceptors and second order neurons. Preparations include retinal slices as well as acute and cultured solitary cells from both amphibian and human retina.
In addition to the interest in understanding normal human vision, we are also interested in treatments for eye disease. We have studied the actions of the phospholipid growth factor, lysophosphatidic acid, on cultured human retinal pigment epithelial cells and its potential role in the pathogenesis of proliferative eye disease. We also collaborate with Dr. Iqbal Ahmad at UNMC in research on the physiology of neural progenitor cells and their therapeutic potential. In addition, we collaborate with Dr. Eyal Margalit in studying the physiological mechanisms by which retinal implants can induce visual perception. The aim of this research is to refine implant design and improve visual perception.
To search for more publications by Dr. Thoreson, visit the National Library of Medicine website.
