More than 100,000 Americans are affected with one of a group of progressive night-blinding disorders collectively known as retinitis pigmentosa (RP). Night blindness refers to difficulty seeing in the dark; it is the initial symptom of RP and usually occurs within the first two decades of life. Within the third decade most patients will also experience some impairment of peripheral, or side vision, which in the majority of instances progresses to a profound loss. In addition, about half of all patients with RP will have variable degrees of cataracts.
The diagnosis of RP is suspected due to a history of night blindness; it is confirmed by measurement of a loss in side vision as well as characteristic pigmentary changes on examination of the retina, the light-sensitive structure that covers the inside of the eye. In very young patients and in some adults who do not demonstrate these characteristic pigmentary findings, an electrical recording of retinal function, termed an electroretinogram (ERG), may be necessary to confirm the diagnosis. This test, in addition to annual measurement of visual acuity and side vision, is also used to monitor progression of the disease in RP patients.
Approximately 50% of patients with RP appear to have an inherited form of the disease. In these patients, it is important to establish a specific genetic type whenever possible, since different genetic subtypes may vary in the severity of visual dysfunction and onset of symptoms. There are three main genetic types of RP possible: X-linked recessive, autosomal dominant, and autosomal recessive. The most severe type, the X-linked (sex-linked) recessive form, is carried by females and transmitted to approximately 50% of their male offspring. The great majority of patients with the X-linked form will be legally blind by age 40, with central vision of 20/200 or worse. (Central vision is the vision used to look straight at an object.) Generally the least severe are the autosomal dominant forms of RP. A patient with this genetic type will, in most instances, have one parent who is affected with RP. The patient, in turn, has a 50% probability of passing on the disease to each of his or her children. For patients with the third genetic type, the autosomal recessive form, an abnormal gene is inherited from both parents who themselves are not affected with symptoms of RP.
A recessively inherited subtype of RP is Usher’s syndrome. This disorder includes RP and a congenital nonprogressive hearing impairment (a loss in hearing present since birth that does not worsen). Approximately 19% of our RP population at the University of Illinois at Chicago were diagnosed as having Usher’s syndrome. As with other types of RP, the cause of Usher’s syndrome is unknown. It is unclear how photoreceptor cells, the cells responsible for vision, deteriorate. However, our laboratory has found an abnormality in male patients with Usher’s syndrome that may be responsible for their ocular and auditory impairment. The sperm cells of these patients demonstrated abnormal motility and structure, which did not result in infertility. The abnormality was in a ciliated structure of the sperm cells, a hair-like structure that is also present in photoreceptor cells and the cells of the inner ear responsible for hearing. We are exploring the possibility that the abnormality in these ciliated structures is responsible for RP and hearing impairment in Usher’s syndrome.
Although there is no definitive therapy available for RP, numerous claims of therapeutic triumphs have been made in the United States and abroad within the last decade. Those approaches receiving the most notoriety are the injection of a yeast-like substance (ENCAD), as proposed in the Soviet Union, and encouragement of a positive mental attitude along with acupuncture. The injection of a product (transfer factor) obtained from white blood cells has also been advocated for treatment of RP. It is important to note that these interventions are not only ineffective but also might be harmful in some patients.
Research toward understanding this disease and developing a treatment is in progress at the University of Illinois at Chicago and other selected centers. At the University of Illinois Drs. Gerald Fishman and Fulton Wong are assessing patients with X-linked recessive RP in an attempt to isolate the gene responsible for this most severe form of night blindness. Once the gene itself is isolated, it will be possible to identify the gene product (abnormal protein or enzyme) that is directly responsible for this retinal disease and its resulting blindness.
Although this defective gene has not yet been found, much progress has been made within the last 20 years in the diagnosis, categorization, and definition of the natural history of RP and other hereditary night-blindness disorders. Other such disorders include choroideremia, which causes degeneration of the choroid (the vascular layer of tissue behind the retina), and gyrate atrophy (ring-shaped areas of thinning) of the choroid and retina. It is anticipated that with time, the field of molecular genetics will afford more insight into the pathogenic mechanisms responsible for these devastating retinal disorders. Once a better understanding of the disease mechanisms is achieved, consideration can be given to effective and safe therapeutic interventions.
The National Retinitis Pigmentosa Foundation Fighting Blindness (1401 Mt. Royal Avenue, Baltimore, MD 21217) funds I I centers that are actively involved with RP research. The University of Illinois Eye and Ear Infirmary has been one of the initial centers funded by this foundation since 1975.
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