Practical Prevention of Nuclear Cataracts 

Tonya An and David Beebe

Department of Ophthalmology, Washington University School of Medicine

  

Cataracts are the leading cause of blindness in the world. Normally, the human lens exists in a hypoxic environment (7-11 mmHg; 1-1.5% O₂) and recent publications have shown that exposure to increased levels of oxygen leads to the formation of nuclear cataracts. The lens lies anterior to the vitreous body, a gel that fills the space between the lens and retina. This gel prevents the circulation of the vitreous fluid and contains high concentrations of ascorbic acid (vitamin C), which helps to consume oxygen released from blood vessels in the retina. Age-related liquefaction of the vitreous gel or retinal surgery, which requires vitrectomy (the surgical removal of the vitreous gel), lower the concentration of ascorbic acid and increase the level of oxygen that reaches the lens. Increased exposure of the lens to oxygen leads to the formation of a cataract (hard opacity) in the center, or nucleus, of the lens. For older individuals, the loss of vitreous gel correlates with the formation of nuclear cataracts and patients who have a vitrectomy develop nuclear cataracts within two years.

My work involves two ways of solving the problem of postvitrectomy cataracts. The first is to minimize the amount of oxygen that enters the eye through the saline solution used during vitreoretinal surgery. Oxygen levels in the reservoir holding the saline solution (Balanced Salt Solution®, Alcon Labs) can be reduced by bubbling nitrogen gas into the bottle. However, measurements taken with an optical oxygen sensor (Oxylab® optode) showed that oxygen diffuses through the tubing that connects the reservoir to the eye. No oxygen-impermeable tubing was available on the market, so I developed a way to cover the tubing with a plastic sheath. By circulating nitrogen gas through the sheath, we are able to maintain oxygen <10 mmHg in the fluid entering the eye. We have applied for a patent for this modification. We received approval for pilot human studies, which will begin later this year.

To prevent longer-term chronic exposure of the lens to elevated oxygen, we are relying on enzymatic reactions. Glucose oxidase converts O₂ and glucose into gluconic acid and hydrogen peroxide. By coupling this enzyme with catalase, which metabolizes hydrogen peroxide, oxygen is degraded to water. Both enzymes were bound to tiny agarose beads (Affi-gel 15®, Bio-Rad Laboratories) and then tested for activity and sustainability. The enzyme-coupled beads lowered  samples containing 38 mmHg oxygen to ~2 mm Hg within 10 minutes. Beads from a year ago that had been stored at -20ºC showed comparable activity to freshly prepared beads and storage of beads at 37ºC for up to one week did not reduce enzyme efficiency to a measurable degree. As a pilot study, the enzyme-coupled beads were embedded in an agarose membrane and we confirmed that this membrane can maintain an oxygen concentration gradient. Our lab is currently working with the Materials Research Department of UC-Santa Barbara to design a synthetic polymer scaffold for these proteins. Our ultimate goal is for this thin polymer membrane to be inserted behind the lens so that oxygen in the vitreous body will be metabolized before reaching the lens cells. We anticipate that these devices can be used routinely to minimize the occurrence of nuclear cataracts after vitrectomy. Modification of the enzyme-coupled membranes may be useful for the prevention of the more common age-related nuclear cataracts that accompany degeneration of the vitreous body.