Darlene A. Dartt

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The tear film: This diagram illustrates the three layers of the tear film and the cells that make them.

Schepens Eye Research Institute Research Responds to the Needs of the Military

The Institute began its collaboration with the Department of Defense (DoD) in the 1990s, thanks to the hard work of Trustee Dr. Donald Korb, who was able to interest the Massachusetts congressional delegation in the research conducted at the Institute that could be beneficial for the military. In 2003 and again in 2005, the Institute held two-day symposia in which practicing military ophthalmologists and optometrists discussed the challenges that they encountered in caring for soldiers injured in the current conflict in Iraq. In turn, the Institute scientists presented their research that had been supported by DoD appropriations and by CDRMP (Congressionally Directed Medical Research Program) grants. The military requirements can be summarized as research to: 1) protect soldiers’ eyes from harm and prevent injuries from becoming blinding, 2) improve treatments in the field, 3) design more effective ways to send medical information with the injured soldier as he moves from a medic’s care in the battlefield to an ophthalmologist’s treatment in a military hospital, and 4) improve rehabilitation of the vision of injured soldiers.

Protect Soldiers’ Eyes from Harm and Prevent Injuries from Becoming Blinding

Use of lasers in the military is growing. Lasers are used as range-finders in guns and artillery and for bomb and missile guidance. The Army is also proceeding with development of lasers as weapons. These powerful lasers would fit into the cargo bay of a plane or a truck. Because of their power, these lasers are designed to destroy buildings, military vehicles, or planes. Another laser under development is a lower-power, hand-held laser that would be used to dazzle rather than blind the enemy. All of these lasers represent a threat to the retina. Because the retina is especially designed to use light for vision, it is exquisitely sensitive to light; laser light is particularly damaging. None of the laser weapons are designed to be blinding, but all could be a threat to vision when used improperly. The Institute has an extensive research program supported by the Department of the Army’s Division on Telemedicine and Advanced Technology Research. Headed by Dr. Dong Feng Chen, a group of Institute scientists -- including Drs. Kameran Lashkari, Andrew Taylor, Bruce Ksander, and Joan Stein-Strelein -- has made laser wounds in the mouse retina to study the response of this model system. The laser itself damages the retina, killing neurons in the area of injury; however, more worrisome damage occurs over time. This collateral damage can be extensive enough to damage vision and cause blindness. Dr. Lashkari found that laser damage appears to release a growth factor in the retina that causes an exaggerated response to the wound. This factor specifically targets the cells that support and nourish the retina. Dr. Chen discovered that the laser light itself damages the nerves in the retina, and that the damage slowly spreads over the next weeks because a special group of retinal cells overreact to the laser damage. Finally Drs. Stein-Streilein and Taylor demonstrated that laser damage to one eye changes the immune response not only of the injured eye, but also to the fellow uninjured eye. Thus both eyes are at risk for loss of vision. This exciting research is continuing, with the goal of developing a drug to prevent the extra damage that occurs to the retina with the laser insult and thus prevent injuries from becoming blinding. 

Improve Treatments in the Field

As seen almost nightly on the news, one of the greatest threats to soldiers and their vision is the improvised explosive devices that can be remotely detonated to cause maximum harm and that are becoming increasingly powerful and causing more extensive bodily damage. The eye is especially vulnerable as it is not protected by the Army’s newly developed body armor. The Institute has several ongoing projects that aid in protecting an injured eye. One such project is a living corneal bandage for the eye. Developing this bandage is the focus of a collaborative research project headed by Dr. James Zieske; his team consists of Drs. Michael Gilmore, Nancy Joyce, and Jeffrey Ruberti (a faculty member at Northeastern University). This bandage is modeled after the living cornea, which consists of three tiers, each containing a different cell type. Dr. Zieske grows the outermost portion -- the corneal epithelium -- which consists of several layers of specialized cells. Drs. Zieske and Ruberti construct the middle portion -- the corneal stroma. Dr. Joyce grows the inner tier -- the single-layered endothelium. One of the challenges for this group is to make a stroma. The structure of the corneal stroma is a unique and fascinating model of cellular engineering. Because the stroma needs to be transparent but -- at the same time -- very tough, the main protein of the stroma is laid down by the stromal cells as fibers of specific dimensions. These fibers are arranged in layers perpendicular to one other with precise spacing between the layers. The cells that produce the stroma are interspersed as a connecting network between the layers of the stroma. Drs. Zieske and Ruberti needed to repeat this elegant and precise pattern. Dr. Ruberti used his expertise as a mechanical engineer to design an apparatus that would spin out these layers with perpendicular alignment. The scientists then added stromal cells; this improvement resulted in a strong, transparent tissue. The stroma itself could be used as a temporary bandage, or the epithelial and endothelial cells could be added. Addition of these cells is the next challenge for this team. Dr. Gilmore’s role in this project is to design the best way for this living bandage to prevent infections from taking hold while it is in place and until the soldier can be seen by an ophthalmologist.

What are Future Institute Projects to Protect Our Soldiers’ Vision?

Over the coming year, Institute scientists are beginning several exciting, new projects in response to the needs of the ophthalmologists of the Armed Forces: In one such project, Dr. Michael Young is designing ultrathin films with special channels and pores that he can seed with adult retinal stem cells and transplant into damged retinas, in an attempt to restore some of the vision that was lost to injury. This project could improve rehabilitation of wounded soldiers’ vision.

Dr. Meredith Gregory-Ksander and Dr. Gilmore are beginning another project --preventing infection to the retina that can occur after trauma. Using different strains of mice, these researchers plan to determine what prevents one strain of mouse from getting retinal infections while, at the same time, the other strain is infected. Once these mechanisms are identified, drugs could be developed that would confer protection to humans. This project would improve treatments to soldiers in the field. 

The inflammation that accompanies injury to any tissue of the body can either be benefical -- preventing infection and promoting healing -- or it can be deleterious and cause scarring.  Scarring is not a dangerous response in most of the body, but it can be devastating in the eye, which depends upon a transparent path for light from the outside of the eye, through the cornea, and all the way to the light-sensitive cells of the retina. If a scar occurs in the center of the cornea, vision is severely worsened. Scars in the retina cause similar loss of vision. In another project, Drs. Reza Dana and Lu Chen are designing a way to promote the benefical effect of inflammation and prevent the deleterious effect. This project would prevent soldiers’ injuries from becoming blinding.

The Institute’s Research for the Deparment of Defense Helps Us All

Most, if not all, of the Institute’s projects for the Department of Defense have important applications for civilians. The living corneal bandage, once perfected, can be used for corneal transplantation and negate the need for corneas donated after death. Corneas from individuals who have had laser vision correction to the eye (refractive surgery) are not suitable for transplantation. Thus the number of corneas available for transplantation is decreasing. Knowledge developed about the response of the retina to laser damage ahould be transferrable to other types of trauma. The treatments designed to prevent laser damage could also be used for many types of ocular trauma. Methods developed to repair damaged retinas using thin films and stem cells could be applied to multiple types of retinal disease including age-related macular degeneration and glaucoma.