B.S. 1983, Univeristy of Victoria; Ph.D., 1987, University of Calgary; Postdoctoral Fellowship, 1987-90, California Institute of Technology

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 new form of treatment, termed "neuroprotection" may provide important avenues of therapy for many neurodegenerative disorders which includes glaucoma.

My laboratory uses transgenic mouse technology to investigate the roles of apoptotic regulatory genes in the process of retinal ganglion cell death. Our current focus is on the functions of the tumor suppressor protein p53, and two antagonistic downstream genes known as Bclx and Bax. Ganglion cells expressing BclX are resistant to stimuli that activate cell death, while Bax is critical for this process. Unfortunately the story is not this simple. We now know that ganglion cells activate different molecular pathways in response to different toxic stimuli and that some of these pathways do not require the functions of these genes. Our goal is to elucidate further the genes involved in these other pathways and then map the critical genes required in the cell death pathway(s) activated in glaucoma.

Nickells RW. Apoptosis of retinal ganglion cells in glaucoma: An update of the molecular pathways involved in cell death. Surv Ophthalmol 43(Suppl 1): S151-S161, 1999.

Li Y, Schlamp CL, Poulsen KP, Nickells RW. Bax-dependent and independent pathways of retinal ganglion cell death induced by different damaging stimuli. Exp Eye Res 71:209-213, 2000.

Schlamp CL, Johnson EC, Li Y, Morrison JC, Nickells RW. Changes in Thy1 gene expression associated with damaged retinal ganglion cells. Mol Vis 7:192-201, 2001.

Borrás T, Brandt CR, Nickells RW, Ritch R. Gene therapy for glaucoma: Treating a multifaceted, chronic disease. Invest Ophthalmol Vis Sci 43:2513-2518, 2002.

Li Y, Schlamp CL, Poulsen GL, Jackson MW, Griep AE, Nickells RW. P53 regulates apoptotic ganglion cell death induced by N-methyl-D-aspartate. Mol Vis 8:341-350, 2002.

Albert DM, Nickells RW, Gamm DM, Zimbric ML, Schlamp CL, Lindstrom MJ, Audo I. Vitamin D analogs, a new treatment for retinoblastoma: The first Ellsworth Lecture. Ophthalmic Genet 23:137-156, 2002.

Audo I, Darjatmoko S, Schlamp CL, Lokken JM, Lindstrom MJ, Albert DM, Nickells RW. Vitamin D analogs increase p53, p21, and apoptosis in a xenograft model of human retinoblastoma. Invest Ophthalmol Vis Sci 44:4192-4199, 2003.