Affiliate Appointments

Eye Research Institute
Institute on Aging
Physiology
UW Comprehensive Cancer Center

Research Interests

• Glaucoma, neuroprotection
• Regulation of ganglion cell death and the role of Bax
• Epigentic changes in apoptotic ganglion cells leading to gene silencing
• Identification of ganglion cell death susceptibility alleles

Glaucoma is one of the leading causes of blindness world-wide. Although an increase in intraocular pressure is often associated with this disease, it is marked by the progressive death of retinal ganglion cells. Previous studies by my laboratory and others have shown that ganglion cell death occurs by a mechanism that is characteristic of apoptosis – a form of programmed cell death that is regulated by a successive activation of genes from within the dying cell. Hypothetically, neuronal cell death can be blocked or prevented by agents that interrupt key biochemical pathways that are controlled by these genes. This form of treatment, termed neuroprotection may provide important avenues of therapy for many neurodegenerative disorders which includes glaucoma.

My laboratory studies some of the earliest events that occur in retinal ganglion cells during the cell death process. For these studies we make use of mice lacking genes critical for the cell death process. Our current focus is on epigenetic changes that lead to silencing of normal gene expression well in advance of the committed step in the apoptotic pathway.

Research Highlights

Dr. Nickells has had a significant impact on the field of glaucoma through the early description of programmed cell death of retinal ganglion cells. This finding launched research to evaluate the molecular pathways activated in dying ganglion cells in efforts to provide therapeutic intervention. Dr. Nickells described surgical crush of the optic nerve to induce retinal ganglion cell death in mice, now considered the gold standard technique used by most laboratories in the field. The technique facilitated research into the molecular pathologies involved in retinal ganglion cell death.  These two groundbreaking publications have been cited over 900 times and have been presented over 200 times.
Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis
Experimental induction of retinal ganglion cell death in mice

T32 Training Area

Development and Diseases of the Anterior Segment

More About the T32 Grant

Education

Postdoctoral Fellowship 1987-1990, California Institute of Technology, Pasadena, CA

PhD 1987, University of Calgary, Alberta, Canada

BS 1983, University of Victoria, British Columbia, Canada