Retinitis pigmentosa is a genetically heterogeneous hereditary disease characterized by impaired functioning of the retinal pigment epithelium with the development of various disorders. The manifestations and severity of symptoms depend on the form of pathology, most often there is a decrease in acuity and narrowing of the field of vision, the development of scotoma and a violation of dark adaptation, blindness may occur in the future. Diagnosis of retinitis pigmentosa is made on the basis of ophthalmological studies (examination of the fundus, electroretinography and electrooculography), molecular genetic analyses. A specific treatment for this condition is currently being developed (gene therapy, the use of stem cells), supportive therapy is used in clinical practice.
Retinitis pigmentosa (retinal pigment abiotrophy) is a hereditary degenerative disease of the retina of the eye, which is characterized by the development of severe visual impairment up to complete blindness. This disease, as one of the causes of vision loss at different ages, has been known since ancient times, but the term “retinitis pigmentosa” was proposed by the Dutch ophthalmologist F. Donders in 1857. With the development of ophthalmology and genetics, it was found out that this condition is a whole set of retinal diseases with different etiologies, but similar pathogenesis. At the moment, several dozen genes and hundreds of variants of their mutations are known that can lead to this disease. The mechanism of inheritance of retinitis pigmentosa can also be different – autosomal dominant, autosomal recessive and X-linked forms of pathology are described. Among the latter, there are also recessive (only men are ill) and dominant (affect persons of both sexes) varieties. The average value of the occurrence of retinitis pigmentosa is about 1:5000, there are forms of the disease with both higher and lower frequency. According to medical statistics, carriers of genetic defects (including asymptomatic carriers) are at least 100-120 million people.
Causes and classification
The etiology of retinitis pigmentosa is very diverse due to the genetic heterogeneity of this disease. Currently, there are a huge number of forms of this condition caused by mutations of various genes. In general, the cause of retinitis pigmentosa is metabolic disorders in photoreceptors and pigment epithelium, which leads to the accumulation of toxic side substances in the retina. The modern classification of the disease is based on the mechanism of hereditary transmission of a genetic disorder, according to this criterion, four main groups of retinitis pigmentosa are determined.
Retinitis pigmentosa with autosomal dominant inheritance is the most common variant of pathology, according to various data, it accounts for 70 to 90% of all cases of the disease. The cause of this form of retinal abiotrophy may be mutations of the genes RP1 (chromosome 8), PRPH2 (chromosome 6), RP9 and IMPDH1 (chromosome 7) and a number of others. All these genes encode proteins involved in the metabolism of the pigment epithelium, so violations in their structure lead to a variety of visual disorders. Autosomal dominant retinitis pigmentosa, despite its high occurrence, is characterized by less pronounced disorders, slow progression, which, with adequate supportive therapy, in some cases can significantly delay or even avoid the development of blindness.
Retinitis pigmentosa with an autosomal recessive inheritance mechanism is a rarer form of the disease. It is characterized by a fairly early onset, rapid course and often leads to complete blindness at a young or childhood age. Its cause lies in mutations of the genes CRB1 (1 chromosome) and SPATA7 (14 chromosome), there are also rarer forms of pathology caused by defects in other genes. The pathogenesis of autosomal recessive forms of retinitis pigmentosa has not been studied enough, it is assumed that the proteins encoded by the above genes are involved in the processes of embryonic development of the visual organs.
Retinitis pigmentosa with X-linked inheritance is also a severe form of this genetic disease. It is most often caused by defects in the RP2 and RPGR genes with a recessive nature of hereditary transmission. For this reason, retinitis pigmentosa of this type affects only boys who do not have a homologous X chromosome. These genes encode proteins-enzymes that take an active part in the metabolism of the retina of the eye, so their defect leads to disorders clinically expressed in retinitis pigmentosa.
Retinitis pigmentosa caused by mutations of mitochondrial DNA is a rare variant of this disease. It is inherited only through the maternal line and is transmitted from the mother to the offspring. Geneticists have not yet been able to identify areas of mitochondrial DNA that undergo mutation in this form of pathology.
There are also other types of classifications of this condition – according to the clinical course, the presence or absence of concomitant malformations, the age of onset of pathology (congenital, juvenile) and a number of other criteria. Currently, there is no single generally accepted classification of this condition, but the separation of all forms of the disease by the mechanism of their inheritance is considered the most convenient and understandable, covering most clinical and genetic varieties of retinitis pigmentosa.
The development of retinitis pigmentosa can begin at any age – recessive and sex-linked forms of the disease most often occur in early childhood, while some autosomal dominant varieties can manifest themselves in adulthood and even old age. As a rule, one of the first symptoms is a decrease in dark adaptation and hemeralopia, which may remain the only manifestation of pathology for several weeks (rapidly progressing forms) or years. With the further course of retinitis pigmentosa, blindness develops at night (nyctalopia) with a normal level of daytime vision. The cause of these manifestations is the predominant degeneration of the rods responsible for light perception in low light conditions.
In the future, retinitis pigmentosa is characterized by narrowing of the visual field and loss of its peripheral areas (peripheral scotoma). This is also a continuation of the destruction of the rods, which are located mainly on the edges of the retina. In severe cases, “tunnel” vision develops, its acuity decreases significantly, patients with retinitis pigmentosa become disabled. Degenerative changes also affect the vessels of the eye, which leads to the destruction of cones, clouding of the lens and vitreous, thinning of the sclera. The combination of these processes leads to complete blindness of the patient. However, not every form of retinitis pigmentosa is characterized by such an outcome – many autosomal dominant varieties of the disease for a long time manifest only hemeralopia and a slight narrowing of the field of vision.
To detect retinitis pigmentosa, an examination of the fundus, electroretinography, electrooculography and other ophthalmological studies, the study of the patient’s hereditary history, molecular genetic analyses are used. If a patient complains of decreased vision in the evening, it is necessary to perform a full ophthalmological examination. On the fundus, individual points (bone spots) located on the periphery of the retina can be detected – they are deposits of fat-like pigment. As retinitis pigmentosa progresses, there are more and more of them, they begin to form closer to the yellow spot. With a pronounced clinical picture of the disease on the fundus, narrowing of arterioles, capillary atrophy, and later – waxy atrophy of the optic disc are also determined.
Measuring the width of the visual fields in retinitis pigmentosa reveals their concentric narrowing of varying severity (depending on the stage of the disease). A characteristic manifestation of this pathology is also a decrease in the sensitivity of blue color up to tritanopia, which is determined using Rabkin tables. The pattern of electroretinography in retinitis pigmentosa depends on the stage of pathology – starting from the reduction of all waves and ending with unregistered ERG in complete blindness. The purpose of electrooculography is to calculate the Arden coefficient, which is normally at least 180%. With retinitis pigmentosa, its value can decrease to 100% or even lower.
Molecular genetic studies are necessary for the final confirmation of the diagnosis of retinitis pigmentosa, in addition, these data may be useful in determining the prognosis of the disease. Currently, methods of genetic diagnosis of the most common forms of pathology caused by mutations of the genes RP1, RP2, RPO, CRB1, SPATA7, RPGR and a number of others are available in laboratories. These studies cover approximately 70-80% of all cases of retinitis pigmentosa, but genetic diagnostic methods have not been developed for numerous rarer forms. As a rule, the diagnostic technique in this case is reduced to direct or automatic sequencing of the sequence of the above genes.
Treatment and prognosis
At the moment, specific methods of treatment of retinitis pigmentosa are under development and clinical trials. There are promising results of the use of gene therapy, stem cells and other medical techniques. In clinical practice, only supportive treatment is used, aimed at slowing the progression of manifestations of retinitis pigmentosa. For this purpose, vitamin A preparations are used, means that improve the trophism of the retina and other structures of the visual organs. In some countries, retinal prostheses have been developed, their implantation has a positive effect on the visual function of patients with retinitis pigmentosa. However, in many cases, especially with autosomal recessive and sex-linked forms of the disease, despite all therapeutic measures, irreversible blindness develops.
The prognosis of retinitis pigmentosa is generally considered unfavorable, since the disease is steadily progressing, eventually leading to complete blindness. In different forms of this condition, only the rate of increase in symptoms differs – it is higher in autosomal recessive varieties and significantly lower in dominant types of pathology. Supportive treatment can delay the onset of blindness by an average of 5-10 years, but there are no other therapeutic measures in clinical practice regarding retinitis pigmentosa today. Prevention is possible as medical and genetic counseling for parents at risk (patients with retinitis pigmentosa or its presence in close relatives). It is also recommended to use sunglasses, which, according to some reports, slow down the progression of symptoms of the disease.