Transgenic Animal Models for the Study of Inherited Retinal Dystrophies

The retina is a complex tissue in the back of the eye containing the rod and cone photoreceptor cells and a network of interneurons that transfer visual information to the brain. The retina is susceptible to a variety of diseases that can lead to compromised vision or blindness. A significant fraction of retinal diseases has been established to have a clear genetic basis. The inherited retinal degenerations are typified by retinitis pigmentosa (RP), an affliction characterized by the gradual breakdown and degeneration of the photoreceptors. This group of debilitating conditions affects approximately 100,000 people of all ages in the United States (NIH 1998). In the elderly, the leading cause of visual loss is age-related macular degeneration (AMD), an eye disease of the macula, a small area in the retina that is responsible for the central vision used in high-resolution activities such as reading, sewing, and driving. A person with AMD gradually loses this clear central vision. It is estimated that AMD causes visual impairment in approximately 1.7 million of the 34 million Americans older than 65 yr (NIH 1997). These inherited diseases are progressive, and no therapies are in clinical use at the time of this writing (NIH 1998). There is a critical need to achieve a better understanding of the disease mechanism in these dystrophies in order to design rational therapies. To this end, a major research effort is under way to identify the cellular, molecular, and systemic factors involved in the pathophysiology of these diseases. Laboratory investigations are using many different approaches, including epidemiology, morphology, cell and molecular biology, and genetics.