Research Highlight December 22, 2015

Identifying new models for human eye diseases

Although it is difficult to measure the impact of chronic conditions like eye disorders, Prevent Blindness America estimates that eye disorders and vision loss cost $139 billion in 2013, placing these conditions among the most expensive health disorders in the US. As the population ages, the number of individuals with eye and vision problems will continue to increase. Therefore there is a great need for vision research and animal models in which to study these disorders.

In an article published the week in the journal Human Molecular Genetics, Gayle Collin, working in the laboratory of Patsy Nishina at the Jackson Laboratory in Bar Harbor, describes a new murine model of the human vision disorders. The mice were identified from the Translational Vision Research Models Program, which uses chemical mutagenesis to screen for genetic cause of ocular disease. The mice had a mutation that introduced a premature stop codon in the gene ADAMTSL4. This gene encodes for a scaffold protein of the extracellular matrix responsible for the correct placement of the lens in the optic path. In humans, mutations in this gene are linked to ectopia lentis (EL) and EL et pupillae, as well as congenital abnormalities of the iris and refractive errors that lead to early-onset cataracts. Using histochemical analysis and electron microscopy the authors determined that homozygous mutants of ADAMTSL4 recapitulate the phenotype observed in human EL patients. In general, murine eyes appeared normal at birth, but progressively worsened as the mice aged, similar to many age-related vision loss disorders. Interestingly, both eyes were not always similarly affected. Although all homozygous mice eventually displayed the phenotype in at least one eye, there was variation in the severity of the phenotype between eyes. This may hint at compensatory mechanisms to accommodate the loss of the ADAMTSL4 protein.

 This article outlines new insights into the pathogenic event that underlie EL and other ocular diseases. Further characterization and investigation of this model will likely provide important information about  human eye health and disease.