A virus “squatter” of neurons that causes havoc to the aging eye.
Getting old is bad enough:- Our bodies don’t work quite as well, and a host of afflictions start to creep up on us as we enter our “elderly” years. Several will affect vision and how well we see the world. We may even develop more serious diseases such as cancer, that need aggressive treatment that lowers our bodies’ immune defenses. The last thing we need is the awaking of a virus that we acquired as children to cause a disfiguring and painful skin infection, and that leaves indelible footprints that affect quality of life and often vision for months, years and even the remainder of life.
That virus is Varicella zoster virus (VZV), a common human herpesvirus acquired by most of us during a bout of chickenpox during childhood. From that point on, we are stuck with VZV for life, where it hides in our sensory neurons for decades with no sign or indications of presence. However, for about 1 in 5 people, mostly as adults over 60 or those undergo immune suppression due to cancer treatment or organ transplant, the dormant VZV awakens to cause Herpes zoster (or “shingles”), Zoster becomes a disease to be feared. The lesions are disfiguring and nearly always painful. Many patients develop a long term form of severe pain (known as post herpetic neuralgia, or PHN) that becomes protracted, debilitating, and is often untreatable. Zoster may leave behind other footprints of neurological disease, such as strokes, ocular tics, palsies and even paralysis. All may lower the quality of life.
Zoster can be devastating to vision. Problematic hard-to-treat eye infections follow zoster on the head that may end in rapid retinal damage, cloudy corneas, persistent ocular pain and blindness. The cornea may be left totally numb, so that it becomes easily damaged by eye droppers or scratches. Treating the consequences of VZV and its long term effects to visual acuity can be difficult and this drives our research. Preventing such consequences is also our mission. While there are vaccines for both diseases, the vaccine for zoster is not well accepted and is only partially effective, meaning that zoster will remain a common affliction for many years to come. Our research aims to understand how the VZV virus causes zoster, and how we can better treat the many consequences.
Our mission is to address how VZV hijacks the neuron as its hideout, what causes its awakening, why this leads to so much pain and neurological problems. We have further developed an animal model of pain in which VZV temporarily causes signs of pain similar to those seen in zoster patients with post herpetic neuralgia. Using this model, we developed and refined new treatment strategies to alleviate VZV induced pain without use of drugs and their side effects. Our approach involves gene delivery of pain blocking modulators to the neurons where VZV remains after chickenpox, and initiates the damage leading to pain. We have also identified several of the viral factors that lead to nerve damage and pain. Finally we have developed a new nerve culture system using stem cells to examine for the first time how the virus travels in human nerve axons to and from the skin and spinal ganglia. This system is being used to search for blockers of virus transport that would prevent VZV from entering latency or causing zoster. The translational consequences could be developed into treatment for Zoster and PHN patients.