A Comprehensive Review of Molecular Biology and Genetics of Cataract

Abstract

Cataract is one of the oldest diseases. Even in the 21st century, the disease is often neglected and treated as an insignificant threat. Although the facts and figures account for the opposite, it is found that globally cataract holds for more than 50% of blindness. Cataract is also one of the first five immediate focus areas of a global Initiative called 'Vision 2020', which intends to eradicate preventable blindness by 2020. The disease is termed as multifactorial; has various extrinsic environmental and intrinsic cell biology factors determining its progress. Over the years, enormous progress has been made towards cataract including the identification of its risk factors. Yet the current scientific knowledge is far from developing a proven preventive or pharmacological strategy for it. The surgical method has been the only way to cure cataract by far. In this paper, we tried to give a comprehensive bird eye view for the disease; we have (a) reviewed briefly the recent progress in delineating the molecular biology and risk factors of cataract (b) delved into genetics of the cataract and overviewed crucial gene families related to the disease identified through single-gene mutations and Genome-Wide Association Studies (GWAS).

GWAS of cataract in Puerto Ricans identifies a novel large-effect variant in ITGA6

“…The symptoms of cataract include blurred or hazy vision, reduced color intensity, increased sensitivity to glare, difficulty seeing at night, and changes in refractive error (National Eye Institute: Cataracts). Cataracts typically occur as an age-related disease, but may also be inherited with an early onset in association with DNA or protein damage which affects lens proteins and aquaporins (Wasnik, H. et al, 2021). Other risk factors include diabetes, certain medications, smoking, alcohol consumption, exposure to ultraviolet radiation, and nutritional deficiencies (National Eye Institute: Cataracts).…”

Identification and Functional Characterization of Mutation in FYCO1 in Families with Congenital Cataract

“…CC shows complex heterogeneity because it is highly divergent with variable inheritance patterns [ 10 ]. Although the prevalent inheritance pattern of CC is autosomal dominant, it can be autosomal recessive or X-linked in rare cases [ 11 , 12 ]. In 50-63% of CC, the etiology is idiopathic, while 30% are monogenic with autosomal dominant pattern [ 12 ].…”

“…In 50-63% of CC, the etiology is idiopathic, while 30% are monogenic with autosomal dominant pattern [ 12 ]. To date, more than 1400 etiologic variations have been described for this disease [ 11 , 13 , 14 , 15 , 16 ]. Non-syndromic cataract is linked to 39 causative genes or loci.…”

“…Autosomal recessive CC has been mapped to 14 loci, but the genes for some loci have not been identified yet [ 14 ]. Several causative genes of CC include EPHA2 (OMIM 176946), GJA8 (OMIM 600897) , FOXE (OMIM 601094) , FYCO1 (OMIM 607182) , GCNT2 (OMIM 600429) , AGK (OMIM 610345) , AKR1E2 (OMIM 617451) , RNLS (OMIM 609360) , HSF4 (OMIM 602438) , LIM2 (OMIM 154045) , CRYBA1 (OMIM 123610) , LSS (OMIM 600909) , CRYBB3 (OMIM 123630) , and GALK1 (OMIM 604313) [ 11 ]. FYCO1 is the most frequent genotype of CC in Pakistani families [ 8 , 11 ].…”

Zinc and Copper Ions Induce Aggregation of Human β-Crystallins

“…Cataracts remain one of the leading causes of blindness worldwide, affecting more than 90 million people [1][2][3]. There are several risk factors associated with cataract formation, such as UV radiation, smoking, and diabetes, among others [4][5][6]. In recent years, metal ion exposure has been recognized as a risk factor, capable of causing protein aggregation.…”