Who Let the Cataract Out of the Bag: Diagnosis and Risk Factors

PREVIOUS PAGE

CRYSTAL CLEAR: THE FUNCTION OF CRYSTALLIN PROTEINS

Cataracts have been known and operated on since before 500 B.C. Cases have been reported for centuries. Earlier referred to as lens opacities, cataract has a Latin root meaning waterfall. The first written account of cataracts and their surgery was in 500 B.C. by Indian surgeon Sushruta. After this, most accounts were from doctors recounting cases they had observed or surgical procedures, with no official diagnosis as observed 1. In the 1800s and early 1900s it was known that cataracts caused double vision and blurry vision by blocking the eye, but not much else was known besides that. They saw some heredity patterns in families, but were not able to make broad connections about the significance of them. 

Cataracts are categorized as lens opacities due to the white aggregate that forms and blocks the ability of the lens to reflect light onto the retina as displayed in Figure 1. This is due to the collection of crystallin proteins in the lens. This can be very easily identified in the clinic by a slit lamp examination. There are many indicators of cataracts besides its physical appearance. They can have severely extreme effects on vision as it is the number one leading cause of blindness in the world. Cataracts are marked by double vision, decreased visual acuity, dimmed lights, decreased night vision, and sensitivity to lights. Although cataracts do not affect other parts of the body themselves, they cause many crashes and accidents yearly. Cataracts themselves can be a cause of other inherited or genetic diseases such as diabetes and Lowe’s syndrome2

Figure 1. Healthy vs cataractous eye, showing a clear pupil on the left and one with an aggregate on the right3.

90% of people are predicted to have cataracts over the age of 75 in their lifetime, and these numbers are only increasing4.

Congenital, juvenile, and age-related cataracts are categorized by their onset. Congenital occur within the first year of birth, juvenile after birth, and age-related symptoms usually appear after the age of 40. Congenital cataracts are anywhere from 9% to 25% incidence of inheritance, as well as some occurring from medications or infections from the mother5

As the crystallin proteins have to last your whole lifetime and are not regenerated, post-translational modifications are one of the main causes of age-related cataracts. Over time, covalent modifications to the proteins prevent them from folding correctly, causing them to become insoluble in the cell and forming aggregates which scatter light incorrectly in the lens. These can occur to any of the crystallin proteins4. However, if α-crystallin is targeted, it is unable to correctly refold or send other proteins for degradation, only enhancing the cataract formation. Since there is only so much to go around, it increasingly becomes a problem for the eyes. 

Although age-related cataracts are mostly due to modifications over time, there are epidemiological and environmental factors which affect the health of the eyes. Nutrition and general health play a large part. UV radiation, smoking, alcohol consumption, and the intake of antioxidants all have an association with cataracts2

Glycation is one post-translational modification that can occur when a sugar becomes attached to the protein product. As sugars are typically bulky molecules, this can affect the proteins tertiary structure and solubility. UV radiation increases the synthesis of advanced glycation end products and increases cross-linking in the lens proteins6

It has been shown that smokers are one to three times as likely to form cataracts than non-smokers depending on their use and cessation7. Largely, the reactive oxygen species caused by the ingredients in tobacco and smoking contribute to the damage of the proteins, preferentially interactive with cysteines and methionines due to their sulfur groups8.

Alcohol has an increasing risk of cataracts as the number of alcoholic beverages a day are increased9

Similarly to the risk of smoking, antioxidants can help reduce the number of reactive oxygen species that cause damage to the crystallin proteins. This is true for ROS causing damage to molecules in any part of the body. In particular, vitamin C and vitamin E are important antioxidants. In addition, I am sure that you have been told carrots are good for your eyes. Whoever told you that wasn’t wrong! Carotenoids are pigments that can promote eye health. Both carotenoids and vitamins can be ingested in the correct dosages with enough fruit and vegetables2. Carotenoids are red pigments can offset the blue light given off by computer and phone screens which also cause oxidative stress to eye proteins10.

Even though there is no direct way of preventing cataracts, just living a generally healthy life will help you. 

References

  1. Stratford 1828
  2. AOA.org https://www.aoa.org/patients-and-public/eye-and-vision-problems/glossary-of-eye-and-vision-conditions/cataract
  3. Thind Eye Hospital https://www.thindeyehospital.org/cataract-and-your-eyes.html
  4. Bloemendal 2004
  5. Hejtmancik 2008
  6. Linetsky 2014
  7. Flaye 1989
  8. Shalini 1984
  9. Linblad 2004
  10. Dr. Heiting 2020

NEXT PAGE

MECHANISM OF DISEASE

Leave a Reply

Your email address will not be published. Required fields are marked *