The most frequent cause of blindness is the explosive growth of blood vessels near the retina, and scientists may have fingered a key culprit in this process: growth hormone. The findings, reported in today's issue of Science,* might lead to a drug-based alternative to laser surgery, the current treatment for this form of blindness that often strikes diabetics and children born prematurely.
Fifty years ago, doctors found that removing the pituitary gland could restore vision in some blind diabetics. But the loss of this hormone factory--which produces a number of chemicals crucial to metabolism, including growth hormone--makes people tired, intolerant of stress, and susceptible to infections. Nowadays the treatment of choice is laser surgery, but this can partially destroy the retina and decrease peripheral vision, and is not always successful in restoring sight.
Searching for a less risky treatment, a team led by Lois Smith, a pediatric ophthalmologist at Harvard Medical School and Children's Hospital in Boston, starved mice of oxygen, inducing blood vessel growth near the retina, the layer of cells that captures light to form images. Blood leaking from the new vessels blocks light from reaching the retina. "Even more devastating, the leaky vessels form scar tissue, which pulls the retina off the back of the eye and leads to total blindness," Smith says.
Smith's team induced blood vessel growth in normal mice and in mice genetically engineered to express a gene for a protein that inhibits growth hormone. The dwarf transgenic mice had 34% less growth of new blood vessels than controls had. Smith's team next injected the normal mice with MK678, a growth-hormone-suppression drug, and found that it reduced blood vessel growth as much as 44%. Smith suspects that growth hormone triggers blood vessel growth by stimulating another hormone, insulin-like growth factor-I, and indeed, infusing the mice with IGF-I wiped out any beneficial effects of the drug.
Experts applaud the findings. "Before, it was only a guess which hormones were doing the damage," says David Clemmons, an endocrinologist at the University of North Carolina, Chapel Hill. Now, he says, the study "proves unequivocally" that growth hormone is involved. But Smith and others warn that developing a drug to fight this form of blindness won't be easy: Blood vessel growth is required for processes such as wound healing and repairing heart tissue after a heart attack. Thus, any new drug must target growth only in the retina and leave growth hormone to work unmolested elsewhere in the body.