What is Retinitis Pigmentosa?
Retinitis Pigmentosa is a group of inherited diseases that usually starts with night blindness, followed by progressive loss of peripheral vision, leading to blindness.
It causes the progressive deterioration of specialised, light-absorbing cells in the retina. The majority of people with Retinitis Pigmentosa are legally blind by the age of 40, with a central visual field of less than 20 degrees in diameter.
An estimated 1.5 million people worldwide are affected by retinitis pigmentosa. Retinitis Pigmentosa is the most common of the retinal degeneration. It has a worldwide incidence of 1:5000 with from 1:4000 to 1:7000 showing great ethnic variability with the highest incidence among the Navajo Indians at 1:1878.
The term Retinitis Pigmentosa includes a wide spectrum of disorders with diverse genetic (chromosomal) findings. Primary cases include those in which the disease process is confined to the eye alone. Syndromic cases include those in which the ocular degeneration is associated with abnormalities in 1 or more organ systems. Around 13 Syndromic Retinitis Pigmentosa may be multifactorial, involving the interaction of genes and the environment. Most syndromic cases are inherited via an autosomal recessive pattern.
Retinitis Pigmentosa is a diagnosis given to people with a certain group of symptoms (see clinical history) and a certain group of signs seen when we examine a patient. The name ‘Retinitis Pigmentosa’ describes what we see when a patient is examined on the slit lamp.
There are mottling and granularity of the retinal pigment epithelium, attenuated (skinny) blood vessels, ‘bone spicule’ collections of pigmentation within the retina especially in the middle ring of the retina i.e. neither at the macula in the central area or in the far outer retina nearer the front of the eye. The optic nerve head is pale. The retina is thinned so the vessels of the choroid are easily seen. The pigmentation is left over from the disintegrated retinal pigment epithelium (RPE) cells and accumulates around blood vessels. This is the feature that gives these diseases their collective name ‘pigmentosa’.
Courtesy of Retina Image Bank
Note the very pale thin retina. The large red streaks radiating outwards are the blood vessels of the underlying choroid showing through. The black pigment clumps are called ‘bone spikules’. The darker orange part in the centre of the photo is the macula, which has still got normal retina present.
Clinical history
There is progressive night blindness and loss of peripheral vision ( the outer rim of the vision) and affects central vision late through deterioration in cones or early due to Cystoid Macula Oedema, diffuse leaking of the retinal blood vessels, RPE defects in macula and the formation of scar-like tissue in the macula. Those people with autosomal dominant Retinitis Pigmentosa are more likely to retain some of their central vision than those with autosomal recessive or X-linked genotypes (Ryan et al., 2013).
Onset varies with genotype from infancy to late adulthood.
Associated Eye Conditions
People with Retinitis Pigmentosa are more likely to also have:
cataracts
myopia
astigmatism
abnormalities of the vitreous
cystoid macula oedema
cellophane maculopathy
increased leakiness of blood vessels which may cause an increased response to eye surgery or trauma
small cup to disc ratio making diagnosis and management of glaucoma challenging
The Disease Process
The many mutations that constitute the group of diseases called Retinitis Pigmentosa, affect cells or their function from the beginning to the end of the long and complex chemical changes that occur in order to change light into electricity. This is known as the ‘phototransduction cascade’.
They can also affect the way the cells of the eye absorb and use vitamin A. The affected gene may affect the way a cell is built (it’s anatomy) e.g. the fine network of proteins inside cells (cytoskeletal-literally the skeleton of a cell) that help it hold its shape, keeps everything in place and help surface receptors to do their jobs properly. Other genes affect the great myriad of functions of the cells i.e. the way cells work (their physiology). However, the end result of all these different mutations, usually only one per patient is the same. Retinal cells die, retinal blood flow decreases. This may be part of the cause or the effect of the wasting way of the retina.
What Can We Do About it?
Genetics, Environment and Inflammation
We are all subject to our genes, which without great feats of research, technology and genetic engineering, we cannot change once we are born. However, we can change the environment in which we place them thus affecting how they are activated and expressed. This is a concept of epigenetics. It is now known that a vast amount of our genetic inheritance lies dormant until the environment stimulates the genes to be opened up and used. It’s a bit like Sky TV; there are many channels, but what is playing on the screen depends on who’s got control of the remote!
Oxidative stress plays a very important role in this.
Oxidative stress is basically something that occurs as a bi-product of us using oxygen to literally burn fuel in our cells at a microscopic level. To burn a fire in a house successfully i.e. not burn the place down, you need various safeguards in place. These might include a firebox, closing the door when you leave the room, making sure that you don’t leave combustibles on top of the firebox, like your, not-quite-finished, newspaper.
When our cells burn sugars and fats to produce energy, other things are produced too. These include Reactive Oxygen Species (ROS). They are highly reactive and will try to combine with other chemicals in our body including the proteins and fats that we're made of. This damages those chemicals such that they can’t function properly. This is one of the ways that we can suffer from accelerated ageing of our tissues and body. Healthy cells, our liver and whole body have many systems in place to mop up these bits of reactive chemicals. These are called antioxidant mechanisms. They include minerals, vitamins, enzymes, phytonutrients and phytochemicals i.e. non-vitamin chemicals found in the plants that we eat.
We might either lack these antioxidants in our diet or our bodies are creating far too many for example in obesity, diabetes, diabetic retinopathy and in any inflammatory condition or disease in the body including a cold/flu. This uncontrolled inflammation is a key player in altering gene expression.
Genetic testing can be very useful to understand our risk and disease process. It also allows us to take the opportunity to modify our behaviour, our lifestyle and environment that are understood to alter gene expression.
In Retinitis Pigmentosa it is these internal drivers of oxidative stress that is known to rapidly activate immune defence (microglia) in the central nervous system (CNS, which is the brain and spinal cord) which damages the photoreceptor. Interestingly, it is this very same oxidative damage that precipitates immune activation of microglia cells in Alzheimer’s, Parkinson’s, multiple sclerosis (MS), retinal injury including light damage, glaucoma, age-related macula degeneration (AMD) and epiretinal membrane (ERM).
Chronic inflammation is a fundamental mechanism in the progress of Retinitis Pigmentosa. ‘It is logical that anti-oxidants and anti-inflammatory treatment will inhibit the production of inflammatory cytokines, suppress microglia activation and lessen and or delay photoreceptor cell death’ (Yoshida et al., 2013).
‘Neuroprotection may prevent or forestall the progression of RP’ (Xu, 2015). With early intervention of a diet with adequate vitamin A and DHA could slow progression of the degeneration (Hartong, Berson, & Dryja, 2006).
In conclusion, you are not simply a victim of your genes. Your diet, lifestyle and environment are things over which you have power. There is a range of severities within which your eye disease will become; best case or worst case scenario. By controlling for the things that are within your power, your outcome is likely to be wide apart from where you might end up if you choose to grasp the nettle.
References
Hartong, D. ., Berson, E. ., & Dryja, T. . (2006). Retinitis pigmentosa. Lancet, 368(9549), 1795–1809. https://doi.org/10.1016/S0140-6736(06)69740-7
Ryan, S., Schachat, A., Wilkinson, C., Hinton, D., Sadda, S., & Wiedemann, P. (2013). Retina. (S. Ryan, Ed.) (5th ed.). London, England: Elsevier.
Yoshida, N., Ikeda, Y., Notomi, S., Ishikawa, K., Murakami, Y., Hisatomi, T., … Ishibashi, T. (2013). Laboratory evidence of sustained chronic inflammatory reaction in retinitis pigmentosa. Ophthalmology, 120(1), e5–e12. https://doi.org/10.1016/j.ophtha.2012.07.008
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