Retinitis pigmentosa: unfolding its mystery.

Retinitis pigmentosa affects 50,000-100,000 people in the United States and about 1.5 million people worldwide. Patients usually report impaired adaptation, night blindness, and loss of mid-peripheral visual field in adolescence. As the condition progresses, they lose far-peripheral visual field and eventually lose central vision as well. Some patients have become blind as early as age 30. The majority are legally blind by age 60, with a central visual field diameter of less than 20°. Findings on ophthalmoscopy include intraretinal pigment around the mid-peripheral retina, for which this condition is named. Histopathologic examinations of autopsy eyes with advanced stages have shown that loss of vision is due to degeneration of both rod and cone photoreceptor cells (1, 2). Retinitis pigmentosa can be detected in early life by electroretinographic testing. Patients with early stages of this disease have electroretinograms (ERGs) that are reduced in amplitude with delays in their temporal aspects (Fig. 1). ERG amplitudes become smaller as the disease progresses. Abnormal ERGs have been detected in asymptomatic children in some cases .a decade before diagnostic changes are seen on routine ocular examination. Individuals, age 6 and older, with normal ERGs and a family history of retinitis pigmentosa have not been observed to develop retinitis pigmentosa at a later time (2, 3). The common forms of retinitis pigmentosa have yielded to treatment with vitamin A supplementation. In a randomized, controlled trial, the course of retinal degeneration as monitored by the ERG was slower on average among adult patients taking 15,000 international units of vitamin A daily, whereas the course appeared to be hastened by supplementation with 400 international units daily of vitamin E. The mechanism by which vitamin A supplementation slows the progression of retinitis pigmentosa is not known. Vitamin E may have an adverse effect on this condition by reducing the amount of vitamin A reaching the eye, as serum vitamin A levels were observed to be significantly lower in patients taking vitamin E (4). Retinitis pigmentosa can be inherited by an autosomal dominant, autosomal recessive, X-linked, or digenic mode (5). Substantial genetic heterogeneity has been observed in this condition, with over 20 chromosomal loci mapped (6, 7). Mutations have been identified in seven genes (5, 8-15). Four of these genes encode proteins in the rod phototransduction cascade-namely rhodopsin, the a and f3 subunits of rod cGMP phosphodiesterase, and the rod cGMP cation-gated channel protein a subunit. Two of these genes encode proteins involved in maintaining photoreceptor outer segment disc structure-namely peripherin/RDS and rod outer segment membrane protein 1. Mutations in the gene encoding myosin VITa have been found in a form of retinitis pigmentosa with associated profound congenital deafness (Usher syndrome, type I). Mutations in these seven genes together account for about 20-25% of cases of retinitis pigmentosa in the United States. Mutations in the rhodopsin gene account for about 10% of cases in the United States and, therefore, represent the most common cause of retinitis pigmentosa for which a molecular