Steven F Stasheff, MD, PhD

Pediatrics (Division of Neurology)
Assistant Professor
Research area(s): 
Electrophysiology of visual processing, esp. retinal ganglion cells
Summary statement: 

Developmental Mechanisms in Retinal Degeneration

Office phone: 
(319) 335-8250
Office number: 
4184
Office building: 
MERF

My research interests center on the fundamental physiologic mechanisms of neurologic diseases affecting the visual system, and on the role that central nervous system (CNS) plasticity may play in both the pathogenesis and potential treatments for such disorders.  Ongoing investigations aim to better understand electrophysiologic changes that occur in hereditary retinal degeneration, the most common inherited cause of blindness, and also a central feature of many neurodegenerative disorders in children and adults, including those that cause severe mental retardation, motor disability, and seizures.

      Currently proposed therapies for these disorders hinge upon the assumption that even after photoreceptor degeneration, remaining retinal neurons would be able to normally process signals from rescued or replaced photoreceptors, or from direct electrical stimulation.  In fact, significant anatomic reorganization of the inner retina occurs, and recent work in my laboratory has identified corresponding physiologic changes that may involve mechanisms of developmental plasticity.  The lab uses state-of-the-art multielectrode recording to monitor spontaneous and light-evoked activity simultaneously from 30-90 retinal ganglion cells in normal (wild type, wt) mice or those of the well-studied rd1 mouse model of retinal degeneration.  Surprisingly, as the animal becomes blind, retinal ganglion cells do not simply drift into silence as might be expected.  Rather, they develop striking hyperactivity (~10 times normal firing rate) that is sustained for many weeks.  In fact, ganglion cells pass through at least three stages of activity:  1) normal spontaneous "waves" of correlated firing in early development; 2) increasing spontaneous activity with temporary preservation of light-evoked responses, selective for the OFF pathway; then 3) sustained hyperactivity that lasts for months, well beyond the loss of virtually all photoreceptors and light-evoked responses.   

     These striking alterations in inner retinal physiology tell us that in the rd1 mouse:  1) blindness occurs in the face of sustained ganglion cell hyperactivity; 2) these cells remain viable, thus amenable to various treatments, for an extended time despite this activity; 3) ON and OFF responses are differentially affected in early stages of degeneration.    Since photoreceptor loss begins early and progresses rapidly in rd1 mice, it overlaps substantially with a normal developmental period of highly active synaptic plasticity.  Thus, the lab now is comparing several transgenic mouse lines to explore the possibility that developmental plasticity may play an adaptive role in resculpting specific inner retinal circuits such as the ON and OFF pathways.  Other avenues of investigation include dissecting changes in the neural code that rd1 ganglion cells use to communicate with the brain, exploring circuit-level and cellular mechanisms that underlie the alterations in their physiologic activity, and determining how widespread these changes are among other neurodegenerative diseases such as neuronal ceroid lipofuscinosis (NCL) and tuberous sclerosis (TS).

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Stasheff Recent Publications.pdf12.06 KB

“Iowa City is a semi - small town centralized around the University and conjoined Hospital. All of the amenities necessary are easily accessible. Iowa City holds an excellent night life and has an emphasis on local everything (coffee, food, etc..). As UIowa is a large university, there are endless activities to be had. The new rec and numerous trails satisfy your exercise and outdoor craving needs. Coming from the larger city of Pittsburgh, I would equate the cultures as both outgoing and open-minded. A more positive aspect of Iowa City over a larger city is the slower feel to the town. Graduate life can be very stressful, so the safety of the town and lack of a dense population make an already busy life easier to manage. ”