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Neuroprotection


Neuroprotection is a treatment strategy aimed at directly preventing the functional demise and death of neural cells. Current treatments for glaucoma are targeted at lowering IOP to a safe level. These treatments are not effective in many patients and can have unpleasant side effects. Also, in a significant number of patients, the IOP is successfully lowered but retinal ganglion cells still die. For these reasons and to preserve vision in more patients, new treatments that directly protect the retinal ganglion cells and optic nerve are needed.

 



 

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Neuroprotection and Glaucoma

Radiation Treatment: A New Paradigm for Glaucoma Prevention

Neuroprotection and Glaucoma

Gaining a better understanding of the processes that mediate glaucoma will ultimately lead to new treatments and preventative measures. Research into the molecular mechanisms of glaucoma identifies damaging processes and suggests targets for developing new neuroprotective treatments. In glaucoma, neuroprotection is aimed at preventing damage to the retinal ganglion cells and optic nerve. A variety of neuroprotective strategies are being evaluated for glaucoma but none are yet sufficiently tested and refined for mainstream clinical use.

Before evaluation in human patients, a neuroprotective strategy will ideally prove successful in multiple animal models. Our research has identified a number of potentially useful neuroprotective strategies that will undergo further evaluation.  For example, using an inherited mouse model of glaucoma, we have recently shown that genetic inhibition of the complement pathway or inhibition of endothelin receptors substantially lessens the occurrence and severity of glaucoma. We will continue to identify and evaluate new neuroprotective strategies.

Radiation Treatment a New Paradigm for Glaucoma Prevention

We discovered a radiation treatment that protects against glaucoma in DBA/2J mice, a strain that develops inherited glaucoma. Understanding and refining this treatment has great potential to revolutionize glaucoma prevention. A single 4 minute long treatment completely protects the vast majority of mice from glaucoma for life. We documented this effect in large numbers of well-characterized mice. The treatment does not alter IOP elevation and thus protects the cells in the retina and optic nerve. Glaucoma is completely prevented in almost all treated eyes (~96% in initial study). A beneficial effect of treatment including high-dose radiation was unprecedented. We are not aware of any other treatments with such a substantial protective effect.

Due to the robust protective effect on nerve cells, the radiation treatment offers a new tool for studying both mechanisms of glaucoma and neuroprotective measures to prevent glaucoma. Our findings open new research areas to investigate the protective effects of radiation and the use of radiation as a treatment against various diseases in which neurons die. Experiments are underway to understand this neuroprotection.  Understanding the processes by which radiation protects from glaucoma may even provide effective new treatments against human glaucoma that do not require radiation. We are eager to fully understand the protective mechanisms, which may involve different cell types. To extend our initial studies that irradiated the entire body, we collaborated with radiation physicists and engineers to build a specialized instrument for irradiating just the eye.  Using this instrument, we demonstrated that the radiation induces protection through a local effect within the eye, and that local irradiation of just an eye is sufficient to protect that eye from glaucoma. We discovered that a subclass of immune cells known as monocytes enters eyes at a very early stage of glaucoma that precedes neural damage.  These cells may be necessary to initiate or propagate neural damage in glaucoma. The radiation treatment modifies eyes so that these cells do not enter the eye.  Ongoing experiments are aimed at more fully understanding these processes.

Despite these successes, more research is essential before considering tests of our radiation treatment on human patients. Supporting the further development of our new treatment paradigm, a recent epidemiologic study of disease rates in survivors of the Hiroshima and Nagasaki atomic bombs suggests an association between higher-level radiation exposure and lower incidence of glaucoma. Nonetheless, our treatment paradigm remains controversial and nonconventional funding sources including philanthropic contributions are necessary to nurture this critically important research, which offers promise for revolutionary new treatments against human glaucoma.


Genetics of IOP Elevation and Glaucoma     Human Glaucoma Collaborations       Implantable Devices     Neurobiology of Glaucoma


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