Age-related macular degeneration is caused by the development of deposits between the retinal pigment epithelium and its basement membrane, called Bruch's membrane. The material starts as basal deposits and becomes drusen, extracellular deposits of protein and lipids that accumulate and can cause blindness.
In order to prevent the basal deposits from forming, researchers developed an animal model to understand the mechanisms that cause them to form in the first place.
"To better develop treatments for preventing the progression of AMD, we need to understand the real biochemical details of how AMD occurs," said the lead author Eric A. Pierce, MD, PhD, and Associate Professor of Ophthalmology at Penn's K.M Kirby Center for Molecular Ophthalmology.
"To do that, we need a model, and now we have one," he added.
Some forms of macular degeneration are inherited, and one type is thought to be caused by a mutation in the Efemp1 gene.
Researchers created a mouse model of this inherited disorder by introducing the disease-causing mutation into the Efemp1 gene of mice. The resulting Efemp1-mutant mice develop the same basal deposits as people with AMD.
They plan to use the Efemp1-mutant mice to study how basal deposits form and what they are made of. The mice can also be used to test potential treatments to prevent basal deposit formation.
"By making this particular mutant mouse, we've made a model of early macular degeneration that's caused by a mutation we know produces macular degeneration in people," Pierce said.
"We think it's going to be a good model to study the pathogenesis of basal deposits," he added.
AMD is the leading cause of vision loss in elderly people, affecting more than 10 million people in the U.S. and about 50 million worldwide. Although it is a common and debilitating condition, prevention and treatment options are limited because AMD is considered a difficult condition to study.
This is because it develops late in life - patients typically show symptoms of AMD after 60, and the only samples researchers could use for study were from people who died while they had the early stages of AMD, and at that point, the tissue is not useful to study the condition's progression.
Therefore, researchers have now developed a model, which they claim is the first important step in developing treatment for the disease.
The study is published in the October issue of Human Molecular Genetics.