The tip of our optic nerve is typically the first place injured by glaucoma.

Now researchers want to know if the powerful pain medicine (+)–pentazocine can help avoid the damage.

Their focus is astrocytes that normally nourish and protect retinal ganglion cells, at the juncture where the optic nerve sends visual information to the brain so we can see. Glaucoma appears to change the relationship between these two brain cell types so that astrocytes move from supportive to destructive mode.

“The theory is that in glaucoma, through some complicated set of mechanisms that may be dependent on intraocular pressure, the astrocytes may change so that they become toxic to neurons,” said Dr. Kathryn Bollinger, ophthalmologist, glaucoma specialist and retinal cell biologist at the Department of Ophthalmology at the Medical College of Georgia at Augusta University.

“Our thought for how we can better treat glaucoma is to protect the neurons directly,” Bollinger said. “That is what we are trying to do,” she said of therapies that may one day be used alongside existing strategies that work to either increase the amount of fluid drained from or produced by the eye.

Her target in the astrocytes is sigma–1 receptor, or S1R, a protein found throughout the body that is believed to have the innate role of protecting neurons. Research animals with S1R deleted have slow progressing, age–associated death of neurons in the eye that is similar to what can occur in glaucoma as well as death of motor neurons that produce ALS–like symptoms.

The problem in glaucoma appears to be that astrocytes become too reactive and more S1R may be part of the solution. Astrocytes need to be activated following an injury to help neurons recover but when they become reactive they go from being nurturing to noxious, increasing in number but forming disruptive scar tissue. They also begin to release substances like the gas nitric oxide, which is toxic at these higher levels but protective at lower ones, and tumor necrosis factor alpha, a signaling protein that activates inflammation and is implicated in a wide range of diseases.

Bollinger notes that there is no evidence that S1R activity is decreased by glaucoma, rather it’s more likely that the increased pressure increases the amount of SIR needed to be protective. “We do know that if we increase its activity, it appears to be protective,” she said. “The question is how.”

Her research model includes co–culturing astrocytes and retinal ganglion cells from the optic nerve of research animals to learn more about how they interact in a healthy scenario. Her research team also will be taking astrocytes from mice missing S1R and putting them with normal retinal ganglion cells to see how that changes the equation. They’ll then add the pain reliever (+)–pentazocine, which activates S1R, and further examine its impact.

They have shown that exposing astrocytes to proinflammatory signals called cytokines, which are elevated in glaucoma, makes astrocytes very reactive. The brain cells experience changes to their shape, start moving around more and GFAP levels go up. Glial fibrillary acidic protein, or GFAP, is expressed by astrocytes and other cells in the central nervous system and thought to help astrocytes maintain their shape and strength under duress, such as increased pressure. However high levels of GFAP, also associated with traumatic brain injury and stroke, appear to put the brain at risk. So, they will add another cytokine, transforming growth factor beta 1, to get the astrocytes to react and see how the presence and absence of (+)–pentazocine affects reactivity.

The MCG vision research team has evidence that treatment with (+)–pentazocine calms the astrocytes, instead prompting them to release brain–derived neurotrophic factor, known to promote healthy survival of neurons.