My name is Haley Phillippi and not too long ago [2019] I was diagnosed with ocular albinism type 1. For a long time I struggled with my vision because no matter whether or not I wore my glasses, my ophthalmologist could never quite get my prescription to 20/20 and up until that point my vision was never stable. I also experienced a lot of other issues with my eyes that were - and still are - embarrassing to explain, such as my pupils being dilated in broad daylight or my eyes watering and becoming irritated while trying to look someone in the eyes. All of these issues are easily explained by a condition I did not know about for most of my life. Even though ocular albinism type 1 is quite rare, there is still a possibility that there are other people like me who did not/do not know they have this particular disorder. For that reason, I feel it is important to raise awareness about ocular albinism, in case someone else out there is struggling with their vision as well.
Introduction
Most people when asked what they find most attractive in another person, will respond with their eyes being the most aesthetically pleasing feature. While the eyes are often referred to as the window to the soul because they portray our innermost thoughts and feelings (generally, subconsciously!), they are not always so transparent of issues we may be facing involving our vision. According to the 2018 National Health Interview Survey (NHIS), 32.2 million American Adults admitted to having trouble seeing, even while wearing corrective lenses, or to being totally blind. Recent evidence suggests that most common vision problems among children and adults are genetically determined. Currently, there are approximately 350 hereditary ocular diseases documented in The University of Arizona Health Sciences database, including ocular albinism.
Ocular Albinism
Ocular albinism is a genetic condition of eyes that is primarily characterized by reduced pigmentation of the iris and retina. Other symptoms reported with ocular albinism include issues with visual clarity and depth perception. However, because the disease is not influenced by external factors, vision loss will not worsen over time. Ocular albinism does not significantly affect the skin or hair, but the affected individual may have a fairer complexion than other members of the family. There are a couple variants of albinism but the most common type of ocular albinism is type 1 (OA1), also known as Nettleship-Falls type. Other types of albinism are much more rare, such as oculocutaneous albinism type 2 (OCA2), which is inherited in an autosomal recessive fashion.
Type 1
OA1 is the most common type of ocular albinism, affecting approximately every 1 in 60,000 men. It presents even less frequently in women because it is an X-linked recessive disease. Therefore, it generally occurs more often and more severely in males, as they only have one X chromosome whereas females have two X chromosomes. Females can sometimes mask the effects of a mutation on one chromosome by expressing the other if it contains a normal version of the gene. Because males only have one X chromosome, they must express the genes present. OA1 results from a mutated G protein-coupled receptor 143 (GPR143) gene found at Xp22.2 in humans.
Everybody has about the same number of melanocytes, which are mature cells that produce melanin in a membrane-bound organelle, called a melanosome. Melanocytes are found in the hair, skin, eyes, and any other tissues where we see pigment being expressed. GPR143 is exclusively expressed by melanocytes and retinal pigment epithelium, and controls the maturation of melanosomes. A mutation of the GPR143 gene can either alter the morphology of the protein or its function. Mutated GPR143 proteins lead to abnormal juvenile melanocytes that harbor the melanosomes and do not release the pigment. Pigment is essential to proper vision because it affects how our photoreceptors absorb and interpret light signals.
In females, the symptoms of ocular albinism are usually more lax than in males. Females can act as carriers of the mutation depending on the genotype of the parents. A majority of female carriers are observed to express the mutated gene as a form of mosaicism. Taking a step back, human males are heterogametic (XY), which creates a real issue during transcription since females are homogametic (XX). The X chromosome is much larger than the Y chromosome and contains hundreds of essential genes, whereas the Y chromosome only houses a few functional genes that are used for sex determination. In order to maintain a balance of genes between males and females, females must undergo dosage compensation by randomly inactivating one of their X chromosomes in every cell. The inactivation of the chromosome means it will not be transcribed or expressed. Female carriers of ocular albinism may express some normal GPR143 protein. Essentially, female carriers can potentially produce sufficient pigment from the normal copy of the GPR143 gene to compensate for the 1 mutated copy of GPR143, so that they are not largely affected by OA1 and experience detrimental visual impairment.
Currently, there are no verified gene therapy treatments for ocular albinism, but there could be in the near future. According to The Vision of Children Foundation website, Sam Hardage, the Founder of The Vision of Children Foundation states, “Our scientists have found a new way to transfer genetic information into cells using pluripotent stem cells, derived from patients’ own skin cells, and gene editing technology. This groundbreaking new process has the potential to enable scientists to use gene therapy to correct genetic vision disorders and other eye diseases.” In the foreseeable future, this research could eventually lead to a treatment for ocular albinism.
Check out my infographic below for a summary of the aforementioned information and more resources!:
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