Many of you are already aware that genes play a role in determining the hue of your eyes, but the fact is that genetics play a role far beyond than merely the color of your eyes. They are also responsible for inflicting various kinds of diseases, some of them very rare.
According to the National Eye Institute (NEI),
“Over the past one a half decade, NEI supported researchers have been able to identify around 500 genes capable of inducing genetic eye diseases like cataracts, strabismus, glaucoma, corneal dystrophies and retinal degenerative issues.”
This write-up is meant to elaborate on major genetic eye disorders, their causes, how genes play a part in their propagation and if there’s a viable treatment option.
Glaucoma belongs to a group of eye diseases, which result in progressively damaging the optic nerve, the central pathway connecting your eyes to your brain. From receded side vision or peripheral vision loss to eventual blindness, such damage can inflict temporary or permanent harm to your eyes.
In addition to peripheral vision loss, other signs and symptoms of the disease may include excessive tearing, photophobia (abnormal sensitivity to light) and bulging eyes.
Glaucoma usually targets older adults, whereby a host of medical conditions including diabetes mellitus, blood pressure (hypertension) and family history can take effect. However, if the disease appears in someone aged below 40, it is referred as the ‘early onset glaucoma’, depending primarily on heredity.
Genetic Causes of Glaucoma
According to NIH,
“MYOC gene mutations are responsible for about 10% to 33% of people suffering from juvenile open-angle glaucoma.”
For more on types, symptoms and treatments of glaucoma, you may run through ‘Glaucoma – A Glance at a Potentially Sight Threatening Eye Disease’.
Researchers have also observed MYOC gene mutations in some people with primary congenital glaucoma.
One of the major functions of this gene is to instruct the body for production of a special type of protein, ‘myocilin’, also found in certain eye structures known as the ‘trabecular meshwork’ and ‘ciliary body’, responsible for regulation of the intraocular pressure.
Research indicates that myocilin is involved with other proteins to form a protein complex, which cannot be formed due to some mutations. When functional complexes are unable to incorporate the flawed myocilin, it starts getting accumulated in the trabecular meshwork and ciliary body.
This excessive protein is believed to thwart the efficiency of fluid from the eye, which can lead to high intraocular pressure, resulting as the signs of symptoms of early-onset glaucoma.
According to NIH,
“Mutations in the CYP1B1 gene play a part in about 20% to 40% people affected by the primary congenital glaucoma.”
In fact, researchers have also observed such mutations in some people suffering from juvenile open-angle glaucoma. The instructions provided by CYP1B1 gene involve the production of a special type of protein, i.e. cytochrome P450, also found in various structures of the eye including the trabecular meshwork and ciliary body.
A process involved in regulation of the fluid secretion inside the clear covering of the eye, the cornea, is also believed to be affected by the CYP1B1 protein. Excessive production of this fluid can also lead to the development of a high intraocular pressure associated with glaucoma.
There is also a probability of myocilin interacting with the CYP1B1 protein. In fact, mutations in both the CYP1B1 and MYOC genes increase the prospects of developing glaucoma at an earlier age with much severer symptoms than in those having mutations in only one of the genes.
2: Congenital Cataracts
Cataracts refer to the opacity of lens within your eye, making it difficult for you to see things clearly, presenting you a foggy or clouded view of the world around you.
The type of cataract that is present at birth or gets developed during the early phase of childhood is commonly referred as congenital cataracts with an estimated prevalence between 1-6 cases per 10,000 live births.
Congenital cataracts can affect one eye as well as both, being referred in such cases as unilateral or bilateral, respectively.
According to a publication in NCBI,
“Approximately half (50%) of all cases of congenital cataracts are believed to be caused by a genetic mutation, with all such cases reflecting quite varied behavior”.
Genetic Causes of Congenital Cataract
Though there can be various factors leading to a congenital nuclear cataract, but genetic mutations remain the most significant ones. Researchers have been able to identify several classes of genes involved in encoding proteins like crystallins, aquaporin, lens-specific connexins, developmental regulators and cytoskeletal structural proteins. With all three types of Mendelian inheritance reported for cataracts, autosomal dominant transmission turns out to be the most frequently affecting one.
3: Retinitis Pigmentosa
Retinitis pigmentosa (RP) refers to a group of related eye diseases responsible for causing progressive vision loss. Retina, light-sensitive tissues lining the back of the eye, is the primary target of the diseases associated with this group. Vision loss in people affected by retinitis pigmentosa happens due to a gradual deterioration of retinal tissue.
Night vision loss is one of the initial signs of RP, becoming apparent during childhood and making it difficult for the victims to navigate in low light conditions. Further on, blind spots start to appear through your field of vision, mostly leading to tunnel vision or peripheral vision loss.
In most cases, it takes years or even decades before RP can affect your central vision, which is required for performing detailed tasks like reading, driving and recognizing faces. Many people suffering from the disease end up as legally blind through their adulthood.
Retinitis pigmentosa is referred to as ‘nonsyndromic’ when it occurs by itself. Research has led to the identification of various major types of nonsyndromic RP, mostly characterized through their pattern of inheritance, i.e. autosomal recessive, autosomal dominant or X-linked.
Though less common, this disease also exists as a part of syndromes capable of affecting tissues and organs other than eyes as well. This form of the disease is referred as ‘syndromic’. Usher syndrome is one of the most known examples of syndromic retinitis pigmentosa, a condition in which a person’s suffers collectively from hearing loss as well as vision loss. Its symptoms are known to be manifested through early childhood.
Genetic Causes of Retinitis Pigmentosa
Researchers have been able to identify over 60 genes associated with causing nonsyndromic retinitis pigmentosa, 20 of them associated with the autosomal dominant form of this genetic eye disorder. About 20% – 30% of all cases of autosomal dominant RP result from the mutations in the ‘RHO gene’.
Similarly, the autosomal recessive form of this disease is associated with a minimum of 35 genes, the most common of which is ‘USH2A’. About 10 to 15 percent of all cases of autosomal recessive retinitis pigmentosa occur due to mutations in this gene.
As of X-linked form of RP, mutations in at least 6 genes can lead to this form of the disease. Mutations occurring ‘RPGR’ and ‘RP2’ gene collectively account for majority of X-linked RP cases.
Two types of photoreceptors constitute the retina, rods and cones, whereby rods assist you see things in low light and cones serve are responsible for how you see things in bright light, including color vision.
Any mutations in genes associated with RP lead to a gradual deterioration of rods and cones in the retina. Progressive degeneration of these cells continuing over a period of time leads to a characteristic pattern of vision loss in the victims of this disease, affecting rods in their retina earlier than the cones. That is why night vision impairment is usually considered as the initial sing of this disorder, whereas daytime vision takes a hit later on when rods and cones both are damaged.
There are some genes associated with RP that also play a part in other eye diseases; for example in a condition known as ‘cone-rod dystrophy’. Perhaps that’s why the signs and symptoms of cone-rod dystrophy bear a similarity to those of RP. However, in cone-rod dystrophy, cones start to deteriorate earlier than the rods, affecting daylight and color vision before tinkering with the night vision.
4: Juvenile Macular Degeneration
Juvenile macular degeneration, also known as JMD, is a collective name given to a group of rare and inherited eye diseases, which target the visual capability of children and young adults. Just as age related macular degeneration (AMD)affects older adults, JDM primarily targets the vision of children, teens and young adults.
Though a rarity (1 in 20,000 cases), the vision of children and teenagers is also affected by macular degeneration, the condition referred as the ‘Juvenile Macular Degeneration’.
Stargardt’s disease, Best Disease and Juvenile Retinoschisis are the major eye diseases constituting juvenile macular degeneration. AMD and JMD not only seem synonymous, they work the same way as well, i.e. AMD affects the macula in adults, while JMD affects the macula in children, teens and young adults.
These eye conditions labeled as JMD take effect due to genetic changes passing down in families.
Stargardt Macular Degeneration
The disease is named after the German ophthalmologist, Karl Stargardt, who reported the first ever case of the disease in 1901.
One of the genetic eye diseases, Stargardt’s disease or Stargardt Macular Dystrophy inflicts progressive vision loss by damaging the retina, comprised of light-sensitive tissues lining the back of the eyes. ‘Macula’ is the precise region near the center of the retina that serves as the prime target zone of this genetic eye disorder. Tasks requiring detailed orientation, such as reading, writing, driving, sewing and recognizing faces rely on the optimal functioning of macula.
Stargardt’s disease leads to a build-up of a fatty yellowish pigment (known as lipofuscin) in cells underlying the macula, overtime damaging the cells vital for clear central vision. Late childhood to early adulthood is the time when symptoms of this genetic eye disorder start to appear, and continue to worsen with the passage of time.
Genetic Cause of Stargardt Disease
Scientists have identified the gene mutations in the ‘ABCA4’ gene to be responsible for majority of the cases of Stargardt’s disease. Another gene whose mutations can lead to this condition is the ‘ELOVL4’, but not very often. Both of these genes instruct the production of proteins found in photoreceptor cells of the retina.
One of the major tasks designated to the ABCA4 proteins is the transportation of potentially toxic substances out of the retinal photoreceptor cells. This transportation mechanism is disturbed due to mutations in the ABCA4 gene, which results in accumulation of lipofuscin in the photoreceptor cells, ultimately damaging the macular tissue in the retina.
Similarly, gene mutations in the ELOVL4 gene result in formation of ELOVL4 protein clumps (also referred to as ‘aggregates’) that accumulate and potentially interfere with the functions of retinal cells, ultimately causing their demise.
Best’s Disease (Vitelliform macular dystrophy)
“Dr Franz Best, a German ophthalmologist, discovered this eye disease for the first time in 1905.”
The second most common type of juvenile macular degeneration, ‘Best Disease’ is named after another German eye doctor, ‘Friedrich Best’. It’s also known as ‘Best Vitelliform Macular Dystrophy’ and was discovered in 1905. Though its symptoms start appearing later in adulthood, an eye exam can identify it between 3 years to 15 years.
Genetic Causes of Best’s Disease
Gene mutations occurring ‘BEST1’ and ‘PRPH2’ genes lead to the Best’s disease. In fact, BEST1 mutations induce the Best disease, in addition to some instances of the adult-onset form of Vitelliform macular dystrophy. Moreover, the adult-onset from of vitelliform macular dystrophy can also be caused by gene mutations in the ‘PRPH2’ gene, but no more than quarter of all the cases of this form of the condition are found with mutations in the ‘BEST1’ or ‘PRPH2’ gene. The factor behind the adult-onset form remains unknown in majority of the cases.
X-linked Juvenile Retinoschisis
“1 in about 15,000 to 30,000 people become victims of X-linked Retinoschisis”.
Also known as ‘X-linked Retinoschisis’, young males are the primary targets of this eye condition, getting vision loss any time between 10 years to 20 years of age and remaining stable until they are in their 50s and 60s.
Genetic Causes of X-linked Juvenile Retinoschisis
Most cases of this rare genetic eye disease occur due to mutations in ‘RS1’ gene, responsible for production of ‘retinoschisin, a protein found within the retina. Cell adhesion or the process of organizing and bonding the retinal cells in place is considered to be the primary function of this protein. Due to gene mutations in RS1 functional retinoschisin is either decreased or completely lost, disrupting the organization and maintenance of retinal cells. This leads to the formation of tiny splits (schisis) or tears within in the retina. As a result, a “spoke-wheel” pattern is formed in the macula, which can be observed during an eye exam. About half of the people with this condition, macula becomes the epicenter of such abnormalities, affecting visual acuity, while the other half gets their peripheral vision affected with the schisis occurring in the sides of the retina. There are also some individuals who suffer from X-linked juvenile retinoschisis not because of a RS1 gene mutation, but because of some reason still unknown.
Whether it’s glaucoma, retinitis pigmentosa, cataracts, macular degeneration or any other degenerative eye diseases, all of them inflict irreversible damage to the retina. So, it is highly imperative to get them diagnosed as early as possible, so that ophthalmologists can assist you with the best possible treatment option aimed at slowing down the damage.
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