Diabetic eye disease, glaucoma, optic neuritis, stroke—they all can lead to blindness. Is there a way to prevent, slow down types of vision loss or restore vision that has been lost? Research at Wilmer Eye Institute at Johns Hopkins School of Medicine and the University of Connecticut School of Medicine studied an experimental drug and certain nerves, respectively, to see what can be done to maintain or restore vision.
Experimental Drug Prevents Diabetic Eye Disease
Researchers at the Wilmer Eye Institute studied two diabetic eye conditions: proliferative diabetic retinopathy and diabetic macular edema. Proliferative diabetic retinopathy occurs when too many blood vessels grow on the retina’s surface. This leads to bleeding, retinal detachment and vision loss. Diabetic macular edema occurs when blood vessels in the eye leak fluid. This causes swelling of the central retina, which damages the cells responsible for central vision.
Scientists studied how a compound known as 32-134D affects mouse and human retinal organoids affected diabetic eye disease. This compound prevented diabetic eye disease by decreasing levels of the hypoxia-inducible factor or HIF protein. The HIF protein is a transcription factor protein that can switch certain genes, such as the vascular endothelial growth factor (VEGF) genes on or off in the body. Elevated levels of HIF cause VEGF to increase blood vessel production and leakiness, resulting in vision loss.
Current treatments for diabetic eye disease include the use of anti-vascular endothelial growth factor or anti-VEGF therapies. While anti-VEGF therapies can stop the growth and leakiness of blood vessel, they don’t work for everyone and there are side effects, such as increased eye pressure and eye tissue damage.
Of course, there are concerns about possible side effects when it comes to inhibiting HIF, since it is an important protein. One concern involves toxicity to tissues and organs, but researchers found that 32-134D was well tolerated. When they measured genes regulated by HIF, they found that expression was close to normal levels. This level was enough to halt the creation of new blood vessels and sustain the structural integrity of existing blood vessels. Another positive aspect of 32-134D is that it remained at active levels in the retina for 12 days following a single injection without causing harm to cells or tissues. Of course, additional studies with animal models are needed before moving on to clinical trials.
Nerve Regeneration Research
Mammalian nerve cells don’t regenerate their connections after an injury. When there is an injury to the spinal cord or the development of glaucoma, nerve damage occurs, potentially leading to paralysis or blindness.
However, research has shown exceptions to this rule, particularly concerning nerve cells. Scientists at the University of Connecticut School of Medicine found a small group of nerve cells that could be coaxed to regrow, potentially leading to the restoration of sight and movement.
Nerves have axons, long fibers that connect the them to the brain or spinal cord. They act like wires that conduct electrical signals from various place on the body to the central nervous system. If an electrical wire is cut, it can’t send a signal from Point A to Point B. The same principle applies to the central nervous system: if the axons in the optic nerve can’t reach the brain or the axons from your hand can’t connect to your spinal cord, you can’t see or move your hand.
For many years, it was believed that mammals lacked the immature nerve cells necessary for regeneration. Researchers in the lab of neuroscientist Ephraim Trakhtenberg found neurons that act like embryonic nerve cells. Under the right circumstances, they can be stimulated to regrow axons, potentially healing vision problems caused by nerve damage.
The problem lies in creating the right circumstances. Once the nerve cells’ axon are stimulated, they begin to regrow in the area of injury, but stall before reaching the target. Researchers started examining another cell type, known as oligodendrocytes. These cells make up the insulation for the axon that is myelin. This insulation improves conductivity and prevents the axons from forming unnecessary connections. Axons at the embryo stage grow to full length before they receive their myelin insulation. Scientists discovered that after a nerve injury, cells that apply myelin interact with the regenerated axon soon after it begin growing. This interaction, which happens before the insulation process, is what stalls axon growth. As a result, they don’t reach their target.
Researchers feel that a varied approach is necessary for the axons to work again. Therapies would need to target both the gene and signaling activity within the nerve cell in order for it to grow like an embryonic nerve cell. It would also be necessary to pause the oligodendrocytes from insulating the axon to allow time for connection. Lastly, there would be treatments to encourage the oligodendrocytes to insulate the axon once a connection is established.
“If you succeed in regenerating injured neural circuits and restoring function, this would indicate that you are on the right track toward understanding how at least some parts of the brain work,” Trakhtenberg says.
These research projects show promise in combatting vision loss to diabetic eye disease and nerve damage. They also illustrate the potential for treatments that may one day restore sight and functionality.