Wet, or exudative, AMD causes total blindness just where you most want vision. Dry AMD can harm central vision, but not destroy it. NIH Women's Health Initiative.
Foreseeing a treatment?
The research focus on angiogenesis and immune responses have been transformed
into a frantic search for a treatment. If the immune system is freaking
out, it's tempting to put it out of business. But it may be dangerous
"to start mucking around with the immune system," says ophthalmologist
Martin Friedlander. While some studies indicate that steroid hormones
treatment may slow wet AMD, "If I take someone with [new blood vessels
under the retina] and bash them with prednisone [a steroid with major
side effects], we can get the blood vessels to shrink."
But the side effects of long-term prednisone treatment, he says, are often unacceptable. We don't need to stress that the immune system also protects against trivialities like cancer and infection - key risks after heart transplants, when strong immune-regulating drugs are used to protect the new heart from the immune system.
The inflammatory hypothesis, previously discussed, remains a hypothesis: AMD may also result from damage by free radicals or ultraviolet radiation, or a shortage of blood flow. Still, inflammation is a key possibility, says Friedlander. "It's easy to imagine that, due to aging changes, you begin to accumulate debris" under the retina. Whatever the trigger, he adds, "the end result is that you get atrophy of the RPE [retinal pigment epithelium], dysfunction of associated photoreceptors ... and abnormal angiogenesis [new blood vessels]. That's when the disaster happens."
However, while it's nice to try to interfere with the start of a disease, for diseases that have many separate triggers, it may be better to block the "final common pathway" that actually destroys tissue. In AMD (and diabetic retinopathy), that would mean blocking angiogenesis.
Not wanted: New blood vessels
Drug companies, which think the market for anti-angiogenic
drugs in eye care alone could total $4-billion to $6-billion, are rapidly
putting today's improved understanding of the formation of blood vessels
into clinical trials. Here are some examples.
New blood vessels form from endothelial cells, which use adhesion (sticky) molecules to move around. Blocking an integrin (one type of adhesion molecule) causes endothelial cells to commit suicide. In an animal experiment, the blocking agent interfered with angiogenesis in the retina, Friedlander says.
It all looks so promising that we almost forgot to
mention that many promising medical developments are skewered by too little
effect, or too many side effects. For example, Jayakrishna Ambati, an
assistant professor of ophthalmology at the University of Kentucky, says
that while the idea of blocking growth factors seems more sophisticated
than zapping blood vessel with a laser, it's "very simplistic to say,
'Let's block VEGF.'" For one thing, because normal blood vessels need
the growth factor to keep calm, "It's not going to be a magic bullet that
will target only bad vessels."
Far better, says Ambati, to "affect upstream events." Rather than try to plug Niagara Falls, he'd rather block the tributaries to the Niagara River before it reaches the Falls.
Still, as ophthalmologists debate the best strategy to prevent, block or reverse AMD, one fact is clear. For the first time in history, it's a good time to be an AMD specialist. For the first time, it's possible to hold out hope for patients. "There's optimism in the field, yes," says Friedlander. "There's excitement. Now we have our chance in the clinic."
Take a gander at our AMD bibliography.
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