UW Eye Research Institute
A microscopic image of the retina and optic nerve of a mouse eye. The axons of the ganglion cells (bright red) are the cables that connect the eye to the brain. Other cells are stained blue. As the axons leave the eye and enter the optic nerve (image top toward bottom), they form the optic nerve head. This is likely the first region of damage in glaucoma.While glaucoma can be treated with medication and/or surgery to slow vision loss, it remains a chronic and currently incurable neurodegenerative condition. Basic science researchers like Nickells are studying the mechanisms underlying glaucoma damage and susceptibility to help determine which genetic, molecular and cellular events are directly responsible for the death of one type of nerve cell in our eyes—the retinal ganglion cells. This progressive cell death, a defining feature of glaucoma, may be linked to the high intraocular pressure long identified as the primary risk factor for the disease. Also true of any complex disease, family history is perhaps the second most important risk factor.
Screening for glaucoma is usually performed as part of a standard eye examination, which includes a measurement of intraocular pressure. A certain minimum pressure is required to maintain the shape and size of the eyeball so that it can work efficiently as an optical instrument. Pressure above the norm, but without a corresponding loss of visual field, makes one a “glaucoma suspect” or “ocular hypertensive.” Chronic pressure elevation causing visual field loss due to optic nerve damage, which can be detected during an eye exam, mandates intervention.
Yet lowering eye pressure does not address the fundamental causes of retinal ganglion cell death. It is these essential nerve cells, transmitting electrical impulses via the optic nerve from the retina to the brain, which trigger our experience of sight. When retinal ganglion cells die, vision is impaired. It would therefore be desirable for the next generation of anti-glaucoma agents to function in a way that prevents or delays the loss of retinal ganglion cells.
“Ganglion cell death occurs by a process of ‘cell suicide’—known as apoptosis—whereby key biochemical pathways conspire in a programmed chain of events leading to the cell’s death,” Nickells explains. “We think that new and effective treatments can be developed specifically to interfere with ganglion cell death, providing important avenues of therapy for many neurodegenerative disorders, including glaucoma.”
Understanding the biochemical processes underlying cell death can give access to the suicide program and allow researchers to target a point that could alter the outcome. Pursuing this goal, Nickells’ lab identified the importance of the Bax gene and detected that ganglion cells expressing Bax at a higher level are more susceptible to activation of cell death. (Next)(Previous)