Legacy Research Institute

Transforming medical care through science, technology, and innovation.



R01DA040965: Perineuronal nets and cocaine-associated memories
PI: Barbara A. Sorg, PhD - LRI

Collaborators: LRI (Dr. Barb Sorg); University of Wyoming (Dr. Travis Brown); OHSU (Dr. Sue Aicher).

The proposed studies will assess how specific neurons in the frontal cortex of rats regulate memories associated with cocaine. In particular, we wish to determine how these cocaine-associated memories that develop after repeated exposure to cocaine can be diminished by manipulating a subset of neurons in the frontal cortex. These studies have translational potential in humans because disruption of cocaine-related memories could help break the cycle of relapse.


R21DA047121: Identifying prefrontal cortex neural ensembles in cocaine-associated memories
PI: Barbara A. Sorg, PhD - LRI

Collaborators: LRI (Dr. Barb Sorg); University of Birmingham, UK (Dr. Jonathan Lee); University of Colorado, Boulder (Dr. Michael Baratta).

The proposed studies will assess how specific groups of neurons, called “neural ensembles” in the frontal cortex of rats regulate memories associated with cocaine. Here we will measure which neurons are active when the memory for cocaine is activated so that future studies can be used to disrupt this activation and diminish relapse. These studies represent an initial step toward translational studies in humans because understanding how to disrupt cocaine-related memories could help break the cycle of relapse.


R01EY029087: Sleep deprivation elevates, and sleep alleviates, oxidative stress in the brain
PI: Jonathan Wisor, PhD - WSU

Collaborators: LRI (Dr. Barb Sorg); Washington State University (Dr. Jonathan Wisor).

The major goal of this project is to determine the extent to which PNNs are regulated by sleep and bidirectional effects between oxidative stress and PNNs around parvalbumin cells in the cortex.


R01EY029087: Nerve Head Glymphatics and Debris Clearance in Glaucoma
PI: Nick Marsh-Armstrong, PhD - UC Davis

Collaborators: LRI (Dr. Claude F. Burgoyne); University of California, Davis (Dr. Nick Marsh-Armstrong)

 This project will test the following hypotheses: 1) ONH debris is removed either by astrocytes using glymphatic channels for waste disposal, or, alternatively, by CNS myeloid cells, 2) and the balance of these pathways differs in the ONH relative to elsewhere in the Optic Nerve (ON), and 3) is highly perturbed within the ONH early in glaucomatous optic neuropathy.

R01EY030590: Advancing OCT evaluation to reveal early-stage changes in glaucoma
PI: Brad Fortune, PhD - LRI

Collaborators: LRI (Dr. Brad Fortune); University of Pittsburgh (Dr. Ian Sigal)

Glaucoma is a leading cause of blindness throughout the world. As a chronic disease with no known cure, it is critical to detect and treat it as early as possible, before it causes permanent vision loss. Eye doctors increasingly rely on an imaging technique called optical coherence tomography (OCT) to help evaluate structures inside the eye that are damaged by glaucoma. However, current clinical OCT methods are only sensitive enough to detect damage after it has occurred. In this project, we will advance novel techniques to extract additional information from OCT scans to detect early-stage damage and distress of retinal cells prior to their irreversible loss.

R01EY030838: Retinal Ganglion Cell Dendrite and Synapse Regeneration in Glaucoma: The Role of Insulin Signaling. 
PI: Adriana Di Polo, PhD - U Montreal; Co-PI: Brad Fortune, PhD - LRI

Collaborators: LRI (Dr. Brad Fortune); University of Montreal (Dr. Adriana Di Polo)

Loss of vision in glaucoma results from the death of retinal ganglion cells (RGCs), the neurons that convey visual information from the retina to the brain. RGC dendrites, the fine processes that connect neurons within the retina, retract soon after glaucomatous injury. Here, we propose to investigate underlying mechanisms and strategies that promote RGC dendrite regeneration leading to cell-cell communication and restoration of neuronal function. The results of this project will lead to novel therapeutic approaches for neuroprotection and vision restoration in glaucoma.

R21EY031120: Targeting the diversity of retinal ganglion cells for replacement therapy.
PI: Jason Meyer, PhD - U Indiana; Co-PI: Brad Fortune, PhD - LRI

Collaborators: LRI (Dr. Brad Fortune), Indiana University (Dr. Jason Meyer)

Damage and loss of retinal ganglion cells (RGCs) is characteristic of many disorders of the visual system, with loss of vision resulting from loss of RGC connectivity to the brain. Although amphibians and fish have the capacity to regrow RGC axons and renew a damaged optic nerve, this normally does not happen in the central nervous system of mammals like human beings. Thus, blindness due to loss of RGCs in glaucoma and other optic nerve diseases is permanent. In this project, we will evaluate the ability of human stem cells – reprogrammed to become “replacement RGCs” – to be transplanted, survive and engraft into the retina of healthy and glaucomatous non-human primate eyes. We will also determine whether different sub-types of replacement RGCs have stronger capacity to engraft and survive, thus paving the way toward restoration of vision to those with optic nerve damage.


R34EY031427: 80 Years and Older Vision & Hearing Important Persons Project (80VIP)
PI: Steven L. Mansberger, MD - LRI

Collaborators: LRI (Dr. Steven Mansberger); Washington University, St. Louis (Dr. Mae Gordon); OHSU (Dr. Elizabeth Eckstrom); Southern California Eye Institute (Dr. Rohit Varma); Battelle Inc. (Dr. Lisa John); SASRAC (Dr. Greg Flamme).

This project will develop the infrastructure to evaluate neurosensory loss in community-dwelling adults aged 80 years and older, a key age group that will increase 600% in the next 30 years, an increase faster than any other age strata or minority group. This age group is rarely included in population-based research because of special concerns in this age groups such as health problems, transportation issues, and impaired capacity to provide informed consent. Information from this proposal will develop the infrastructure for a future multicenter study to forecast health care costs, develop novel interventions, and augment healthy living and prevent morbidity such as institutionalized care.