The eye lens fiber cells are composed of high concentration of (>90 %) specific soluble proteins called crystallin. Crystallin protein is classified into three major groups such as α-, β-, and γ-crystallin that act as components of the lens and are vital for lens transparency, viscosity, and high refractive index. The oligomeric α-crystallin molecule exists in dynamic state continuously involved in rapid exchange and dissociation of subunits. The homologous and heterologous interactions of the crystallin proteins within/with other crystallin and membrane proteins are yet another vital factor of lens transparency [11]. They also physically and functionally interact with both the cell membrane and cytoskeleton. Functional changes in α-crystallin have been shown to modify cell–cell interactions and lead to pathology in vivo [12], the well-known examples are various neurodegenerative diseases and cancer. Crystallin proteins are arranged in regular mode with a shorter range order lesser than the wavelength of light. The fiber cells maintain a unique signature of crystallin expression contributing to higher concentration leading to molecular crowding thence enhancing α-/β-, α-/α-, β-/γ-, α-/γ-, and γ-/γ-interactions and associations. It is envisaged that minor encumbrance in the protein–protein interaction phenomenon directly contemplates in lens transparency [4, 13–19]. Number of in vitro and in vivo assays proved that the homogeneous and heterogeneous interaction of α-crystallin prevents the cluster form of aggregates in native as well as different physiological conditions [20]. The highly ordered array in the lens is accountable for refractive index and transparency; this is achieved by the crystallin proteins and characterized for being able to reach in higher concentration without aggregating and scattering light. This highly conserved, small heat shock protein prevents the aberrant physiological changes taking place in the eye lens protein during stress conditions.

Transparency and proper light refraction of the lens depend on a unique arrangement of tightly packed fiber cells, which in turn rely on a defined protein structure. The human lens has a protein concentration of 33 % of its wet weight, which is twice that of most other tissues such as brain = 10 % and muscle = 18 % [21]. The crystallins are intracellular proteins contained within the epithelium and plasma membrane of the lens fiber cells. α-Crystallin constitutes subunits αA and αB; each subunit polypeptide has a molecular weight of about 20 kDa and possesses the ability to form oligomers of 200–800 kDa. The subunits are held together by hydrogen bonds and hydrophobic interactions. Crystallins appear to be specifically involved in the transformation of epithelial cells in the lens fiber cells. At the time of human birth 1.6 million fiber cells are found that increases to 3 million at the age of 20 and 3.5 million at 80 years of age [22]. The rate of synthesis of α-crystallins is seven times higher in epithelial cells than in the cortical fibers, indicating a significant decrease in rate of synthesis after the transformation. β-crystallins account for 55 % (by weight) of the water-soluble proteins in the lens and γ-crystallins are the smallest form of the crystallins, with a molecular weight in the range of 20 kDa. The conversion of water-soluble lens protein to insoluble protein is the indication of cataract during aging process, the acceleration of insoluble protein leads to form protein aggregation. As there is negligible protein turnover in mature fiber cells [23], most of these proteins are surprisingly stable and remain in the lens for the duration of an individual’s life span [24]. Methods have been developed to isolate lens protein, which normally involves sequential buffer extraction from decapsulated lens tissues [24]. Lens proteins extracted by diluted aqueous buffer are termed as water-soluble protein, which accounts for up to 80–90 % of total proteins in normal lenses and consists of almost entirely structural protein known as crystallins [25]. Lens proteins that are solubilized in 7–8 M urea are termed as water-insoluble (WI)/inclusion proteins, which consist of denatured crystallin and cytoskeletal proteins [24, 26, 27]. The insoluble protein fraction possesses high-molecular weight disulphide (S-S)-linked protein aggregates. The urea-soluble fraction (WI) contains cytoskeleton proteins that provide the structural framework of the lens cells and the fiber plasma membranes that resemble erythrocyte plasma membranes in many aspects. As the fiber cells begin to elongate, the MIP can be detected in membranes and throughout the mass of the lens. It is not found in the epithelial cell and seems to be associated with the differentiation of epithelial cells in to fiber cells. The MIP is concentrated in the gap junctions and is the predominant protein of the junction-enriched membrane proteins. It is an inherent part of the membrane, where it can be localized by immunofluorescence.

During stress conditions, over expression of αB-crystallin has been reported in various non-lenticular tissues especially in cardiac and skeletal muscles related to myopathy, carcinoma, and neurodegenerative diseases. αB-crystallin exists as molecular chaperone prevent the misfolding of proteins leading to aggregation and amyloid fiber formation in lens and other organs [28]. Moreover, elevated levels of αB-crystallin confers anti-apoptotic effects in many cells including retinal pigment epithelial cells, and always detected as biomarker of oxidative stress-induced apoptosis [29] in various muscular and neurodegenerative diseases. Researchers have also reported that temperature above 30 °C could enhance the chaperone-like activity of αA-crystallin to several-fold [30] and the protein structural stability persist at 100 °C with little unfolding condition, even though, it will revert back to normal when cooled to 21 °C [31]. Failure of this chaperone activity is mostly due to mutation or alterations during posttranslation modifications in α-, β-, and γ-crystallin and leading to aggregation of misfolded proteins resulting in diseased state [32, 33]. There are lots of ongoing epidemiological studies to figure out risk factors; however, there are only a few factors recognized and investigated in detail like UV-B exposure, low antioxidant intake, certain medications, cigarette smoking, diabetes, and gout as well as family history [34]. In contrast to these age-related forms of cataract, congenital cataracts or cataracts in early childhood are rather rare but avoidable causes of blindness reported in both developed and developing countries with a frequency of 30 cases among 100,000 births; with a further 10 cases being diagnosed by the age of 15 years (mainly as dominant forms). Rates are likely to be higher in developing countries because of Rubella infections and consanguinity for the recessive forms [35].

Congenital cataract is detectable at birth or during the first decade of life due to different causes, including metabolic disorders (galactosemia), infections during embryogenesis [36], gene defects, and chromosomal abnormalities [37]. Cataract may be an anomaly, observed in association with other ocular developmental abnormality, or part of a multisystem syndrome, such as Down’s syndrome, Wilson’s disease, and myotonic dystrophy [38]. Inherited cataracts correspond to 8–25 % of congenital cataract [39] and the commonest mode of inheritance is the autosomal dominant form. Appearance of the lens opacities seen in families with inherited cataract is classified into five groups: lamellar, coralliform, stellate, anterior, posterior polar, and finally an “undefined” group. At least 34 loci in the human genome have been reported to be associated with various forms of pediatric cataract. Autosomal dominant and recessive forms of cataracts have been caused by mutations in 22 different genes encoding crystallins CRYAA [40], CRYAB [41], CRYBA1 [42], CRYBA4 [43], CRYBB1 [44], CRYBB2 [45], CRYBB3 [46], CRYGC, CRYGD [47], and CRYGS [48], cytoskeletal proteins BFSP1 [49] and BFSP2 [50], membrane proteins GJA3 [51] and GJA8 [52], MIP [53] and LIM2 [54], transcription factors HSF4 [55], PITX3 [56], and MAF [57], glucosaminyl (N-acetyl) transferase 2 (GCNT2) [58], chromatin modifying protein-4B CHMP4B [59] and TMEM114 [60] (Table 16.2). On the basis of current studies, mutations in about half of the affected families occurs in crystallin gene, a quarter in connexins and the remaining is evenly split between membrane proteins, intermediate filament proteins, and transcription factors. However, the relative contribution of these classes of genes to pediatric cataracts is still unclear.

Age-related/senile cataract is a progressive disorder of the lens affecting transparency accompanied with marked light scattering. Oxidative stress-related factors, exposure to radiations, smoking, low antioxidant status, and exposure to irradiations are the key factors that trigger cataractogenic process above the age of 60. Free radicals and glycation are the perpetrator causing cross-linking of the lenticular proteins, and the aggregated proteins scatter light. With aging phenomena, the antioxidant defense machinery gets defoliated and the system is overridden by oxidative stress [87], specifically the level of GSH and its precursor amino acids are significantly reduced. The reason for the decline in GSH is possibly the alterations in the function of GSH transporters [88]. In the case of secondary cataract like diabetic cataract, the protein breakdown process is accelerated during hyperglycemia. Aldose reductase facilitates the transfer of glucose into sorbitol, which is impermeable to the membrane; accumulation of sorbitol ends with glycative and osmotic stress [89]. Any injury pertaining in the lens tissue may lead to hydration of the protein causing dense cortical cataract. The extent of opacification depends on the type and depth of injury.

Significant inroads are being made to elucidate the series of changes taking place during the cataractogenic process. The sequel begins with the biochemical or physical insults carried on by phase separation of crystallins into soluble and insoluble aggregates, distortion of antioxidant defense, reduction in GSH level, loss in protein secondary and tertiary structure; any of which may result in light scattering. However, when the key factor reckon to be a mutation in the crystallin gene or maternal malnutrition, this results in congenital cataract. If the factor is an environmental insult such as radiation, hyperglycemia, or oxidation, this may contribute to age-related cataract.

The nature of day-to-day life of individuals and occupational demands plays a vital role to create awareness of visual impairment and management. Cataract (other than congenital form) is one of the leading causes of avertable blindness worldwide. The burden of visual impairment is directly correlated with the loss of productivity. Accumulation of damage from the environment, deterioration of defense, repair mechanisms, and genetic predisposition [104] are the major contributing factors. Limited access to health care, lack of awareness to obtain healthy balanced food, medication, and UV-radiation are considered as a potential ground for visual impairment and increased rates of cataract surgery.