Retinitis pigmentosa (RP) is a disease condition that was first identified and named by Dr. Donders in 1857. Retinitis pigmentosa is a group of related conditions that are inherited, progressive and clinically distinctive and share a similar feature of dystrophy or damage to the photoreceptors of the retina and of the pigment epithelium underneath the photoreceptors.
The normal retina is a layer or membrane that lies at the back of the eyeball. It is a photosensitive layer with millions of photo receptors that are stimulated when light rays fall on them. These photo receptors or rods and cones transmit the information of the light patterns to the brain via nerves that converge to form the optic nerve. This results in normal visual perception.
In Retinitis pigmentosa there are initial vision problems especially in dim light. This manifests as a loss of vision around the peripheries. This is known as tunnel vision. Central vision is spared until the later stages of the disease.
Retinitis pigmentosa is the leading cause of inherited retinal degeneration-associated blindness. The disease process begins with changes in pigment and damage to the small arteries and blood vessels that supply the retina. There may be atrophy or damage to the optic nerve as well. The damage to the pigment epithelium occurs due to pigmentation that begins and settles within the layers of the neural retina.
As the disease progresses there is a thinning of the retinal blood vessels. Gradually the light-sensitive cells of the retina deteriorate. Both rod and cone photoreceptors are affected and the type of genetic defect determines which cells are more affected. Rod photoreceptor malfunction is the most commonly encountered problem in RP.
To date, more than 50 different genetic defects have been identified to be linked with Retinitis pigmentosa. Around 30-40% are autosomal dominant, 50 to 60% are autosomal recessive and 5 to 15% are X chromosome linked (passed from mother to son and carried by daughters to their sons).
The autosomal dominant forms tend to have milder symptoms with onset usually seen at around fifth or sixth decades of life. The X-linked form is the most severe with loss of central vision seen as early as in the third decade of life itself.
Retinitis pigmentosa is the leading cause of inherited retinal degeneration-associated blindness. The prevalence is 1 in 4,000 among all age groups and 1 in 3,195 persons in population aged between 45 and 64. X linked variety affects men more than women and other types have no sex or ethic preferences.
Diagnosis is usually made on the basis of examination of the retina using slit lamp biomicrosopy.
There is no cure for Retinitis pigmentosa and no treatment is known to stop the progressive vision loss in the condition. There are a number of research areas including gene therapy and antioxidant therapies that are being explored in the treatment of the condition.
Retinitis pigmentosa is a group of related conditions associated with progressive degeneration of the light sensitive retina that lies at the back of the eye ball. This layer of photo sensitive cells with photoreceptors called rods and cones is normally associated with vision.
The rod photoreceptors normally provide black and white vision whole the cone photo receptors are associated with color vision. Rods are mostly affected but sometimes the genetic disorder affects the cones as well.
With the course of the disease there is degeneration of the retina and its capability to transmit images of meaningful vision reduces leading to complete loss of vision. Cells from the pigmented layer of the retina enter the layer containing nerve cells leading to typical pattern of black or brown star shape pigmentations in the retina that gives the diseases their name.
Symptoms of retinitis pigmentosa include:-
Retinitis pigmentosa is commonly identified by the examination of the appearance of the retina using slit lamp biomicroscopy. Common findings on examination and steps in diagnosis include:-
Retinitis pigmentosa is one of the commonest forms of inherited retina degenerative blindness worldwide. With the advent of molecular technologies it has become easier to identify the genetic defects associated with this condition.
Over a 100 genetic mutations have been found to affect the inheritance of this condition. Inheritance patterns are responsible for the different types of retinitis pigmentosa.
Inheritance may be:
Autosomal dominant has the maximum possibility of a parent-to-child transmission. Autosomal recessive classification is based on established inheritance between different family groups following principles of Mendelian genetics.
X linked inheritance is of further two types – Simplex and Multiplex. Simplex reflects isolated cases with one affected member. Multiplex is when at least two family members are affected.
There are two types of retinitis pigmentosa depending on relative involvement of rods and cones photoreceptors. Patients with Type 1 RP display early and preferential loss of rod sensitivity and early signs such as diminished night vision. This condition also progresses lowly and leads to a region specific vision loss.
Patients with Type 2 RP have a progressive and combined loss of rod and cone sensitivity with onset in adulthood and later onset of diminished night vision.
Retinitis pigmentosa may of two types - nonsyndromic, or "simple" when other organs are not affected or syndromic where other organs are involved (e.g. Usher syndrome). Nonsyndromic retinitis pigmentosa can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.
There may be a rare digenic inheritance as well. Digenic inheritance is seen in persons with both a ROM1 mutation and an RDS gene mutation. Those with simplex cases result from autosomal dominant or X-linked mutation or autosomal recessive inheritance.
Table 1. Causes of Isolated Retinitis Pigmentosa by Mode of Inheritance
|Mode of Inheritance|| |
Proportion of All RP
Autosomal dominant RP (adRP)
Autosomal recessive RP (arRP)
X-linked RP (xlRP)
Genes associated with retinitis pigmentosa code for proteins that are involved in the visual cycle where the photo reactive pigments are produced and recycled for effective vision. These genes also code for proteins that form photoreceptor structure and photoreceptor cell transcription factors.
Common mutations include those in the RHO gene. This gene codes for the rods and mutations may lead to autosomal dominant RP, autosomal dominant congenital stationary night blindness, or, rarely, autosomal recessive RP.
Similarly mutations of the RDS are also seen. This gene normally codes for peripherin and mutations lead to autosomal dominant RP, autosomal dominant macular degeneration, or digenic RP.
Some common genetic mutations and their associated retinitis pigmentosa types include:-
There are more than 100 RHO mutations and P23H is commonly found in 10% of Americans with autosomal dominant retinitis pigmentosa. RDS mutations may lead to macular degeneration to complex maculopathies. Arg677stop and 2280del5 are the much studied RP1 mutations.