Lens opacification

Lens opacification

Lens transparency depends on the regular arrangement of lens fibers and tight packing of crystallins.

  • 80-90% of soluble lens proteins are crystallins (alpha, beta, and gamma crystallins in decreasing order of molecular weight).
  • The amount of both water soluble and water insoluble proteins increase with age, and the ratio of insoluble to soluble proteins increases after age 50. This causes increased light scattering and promotes cataract formation.
  • Crystallins in the aging nucleus shift to higher molecular weight moieties, which is hypothesized to be the result of protein glycosylation and aggregation as well as the formation of advanced glycosylation end-products.
  • It is not clear the degree to which protein glycosylation contributes to lens opacification.

Opacification and cataract formation is multifactorial and thought to involve oxidative damage, disruption of the ordered arrangement of lens fibers and proteins, and exposure to diseases and medications that place metabolic stress on the lens.

Several small molecule antioxidants, including ascorbic acid, vitamin C, and glutathione, protect the lens from oxidation. Unfortunately, production and recycling of antioxidants decreases with age.

  • Glutathione levels decline drastically in the aging nucleus, which cannot synthesize glutathione. Levels are lowest in lenses with cataracts.
  • Methionine and cysteine are the amino acids most vulnerable to oxidation, leading to methionine sulfoxide and disulfide groups. Protein aggregation through disulfide bond formation leads to creation of high molecular weight insoluble compounds, fluctuations in the refractive index, and lens opacification.
  • Oxidation of membrane lipids is thought to contribute to cataract formation by impairing membrane-associated pumps (e.g. the Na-K ATPase), in turn leading to epithelial cell death and osmotic changes, crystallin aggregation, and lens opacification. This is not a process observed in the normal aging lens.
  • Cigarette smoking is thought to contribute to nuclear cataract formation through induction of oxidative stress.

Damage to calcium homeostatic mechanisms also leads to opacification of the cortex and eventually the nucleus.

Radiation damage contributes to cataract formation by affecting stem cells in the epithelial germinal center zone. The affected daughter fiber cells that migrate to the posterior pole eventually generate feathery or dust-like cataracts. This process may take as long as 10 years after exposure to ionizing radiation depending on the degree of exposure (X-rays, gamma rays, beta rays, and neutrons). UV light is associated with increased risk of cortical cataracts, especially when there is high exposure at young ages.

Many systemic diseases contribute to cataract formation. In diabetes and metabolic syndrome, glycation of ion pumps leads to osmotic stress and cataract formation. Atopic dermatitis, GI diseases, and renal diseases are also associated with increased cataract risk.

Any ocular diseases that interfere with the supply of nutrients and oxygen to the lens (or that increase toxin exposure) can lead to cataract formation. Glaucoma, uveitis, infection, previous ocular surgery, and even severe myopia are known to increase cataract risk. Abnormalities in the lens epithelial stem cells can also lead to epithelial cell migration to the posterior lens, where they can cause opacification.

Ocular trauma can lead to the formation of cataracts and lens dislocations. Blunt force trauma puts pressure along the anterioposterior axis and expands the lens at the equator, shearing lens fibers in the axial region. This can lead to a characteristic stellate- or rosette-shaped cortical cataract. Penetrating injuries can lead either to cortical or whole lens opacifications. Zonules can also break as a result of trauma, leading to phacodenesis and lens instability or dislocation.

Traumatic cataract
Electrical injury cataract