Causes and Risk Factors
Living cells are naturally exposed to free radicals including reactive oxygen species (ROS) (Michael 2011; Colorado State University 2013). Mitochondria (cellular organelles) produce free radicals as a by-product of their normal function (Cadenas 2004). These free radicals can damage other cellular structures such as proteins, lipids, and DNA. Exposure of cells to excess oxidative stress that overwhelms intrinsic antioxidant defenses can lead to cellular dysfunction and destruction (Carper 1999; Uttara 2009). The lens epithelium is particularly sensitive to oxidative stress, and oxidative damage of this layer of cells can result in the formation of lens opacities (Carper 1999; Sharma 2009).
Many diseases are associated with the incorrect folding of proteins as a result of oxidative damage. The three-dimensional structure of proteins dictates their function; therefore, any structural damage to proteins can lead to their malfunction. Since the protein concentration in the lens is the highest in the body, the lens is vulnerable to this type of perturbation (Surguchev 2010).
The transparency of the lens depends on the correct three-dimensional structure of the lens proteins, and protein aggregation in the lens has been linked to the formation of cataracts (Moreau 2012). This is especially true when antioxidant mechanisms fail to prevent oxidative damage, causing a cascade of damage to several types of proteins in the lens (Carper 1999; Babizhayev 2010). One type of lens protein known to cause cataracts when damaged is the crystallins (Sharma 2009). Crystallins provide structural support to lens cells and allow for the optimal bending of light as it enters the lens (Bloemendal 2004; Sharma 2009).
In addition to oxidative stress, studies have uncovered a causative role for another modification, known as glycation, in the opacification of the lens (Swamy 1987). Glycation causes proteins to become damaged and dysfunctional. It is the result of sugar molecules interacting with proteins and modifying their structure. Proteins in the lens, which are among the longest-lived in the body, are particularly susceptible to glycation (Franke 2003).
The result of this interaction is the formation of toxic molecules termed advanced glycation end products, or AGEs. Accumulation of AGEs is associated with several age-related diseases including diabetes, renal failure, and cataracts (Wautier 2001; Hashim 2011; Swamy 1987; Wautier 2001; Franke 2003; Gul 2009). Additionally, AGE accumulation is thought to be directly related to the intensity of yellowing of the lens, which is often observed in cataracts (Shamsi 2000).
In addition to the pathological roles of oxidative stress and glycation in cataract formation, several factors are known to increase cataract risk. Many of the following risk factors are associated with increased glycation and/or oxidative stress.
Age. There is a strong association of cataract development with age and oxidative damage. Since there is no turnover of lens epithelial cells, the accumulation of oxidative damage over many years is an important component of cataract development (Truscott 2005).
Gender. Although cataracts afflict both men and women, a study in an Australian population revealed that 58% of people who have suffered from cataracts are women, and a higher incidence of cataracts in women is supported by studies on other continents (Giuffrè 1995; Delcourt 2000; Kanthan 2008; Mares 2010; Vashist 2011).
Poor Nutrition. Lack of a proper diet and low intake of vitamins, minerals, and antioxidants found in fruits and vegetables predispose people to developing cataracts (Jacques 1988; Bunce 1990; Knekt 1992; Christen 2005; Zhou 2012).
Diabetes. There is a strong association between duration of diabetes and the development of cataracts (Kim 2006; West 2010). In people with diabetes, cataracts may begin to form up to 20 years earlier than in non-diabetics (Hashim 2012). Since diabetes is characterized by elevated blood sugar, glycation reactions occur more rapidly and frequently in this population, which explains a great deal of the association between diabetes and cataracts (Hashim 2011).
Exposure to Ionizing Radiation. Occupational or personal exposure to ionizing radiation, such as X-rays or ultraviolet (UV) rays, is associated with an increased risk of developing cataracts (Worgul 1976; Vano 2010; Varma 2011). In order to decrease exposure of the lens to UV radiation, it is recommended that protective eyewear or sunglasses with UV filters be worn during daylight hours.
Smoking Status and Alcohol Consumption. There is a significantly increased risk for cataracts for those who smoke and among those who drink alcohol heavily (Delcourt 2000; Klein 2003; Jun 2009).
Genetics. When cataracts form in newborns, they are often associated with mutations in proteins involved in metabolic pathways related to the metabolism of a sugar called galactose, while mutations in structural proteins like crystallins occur frequently in childhood cataracts (Churchill 2011; Santana 2011; Chan 2012; Clark 2012).
Additional factors have been implicated in the development of some types of cataracts, but more studies need to be conducted to determine the strength of these relationships (Heiba 1995; Merriam 1996; Sanderson 2000; Zhou 2007; Jun 2009; Hashim 2012; Worgul 1976; Alapure 2012; Paine 2010; Tsai 2003; Vano 2010):
- Imbalanced calcium ion signaling
- Long-term steroid (glucocorticoid) use