Molecular Processes Implicated in Human Age-Related Nuclear Cataract

Abstract

Human age-related nuclear cataract is commonly characterized by four biochemical features that involve modifications to the structural proteins that constitute the bulk of the lens: coloration, oxidation, insolubility, and covalent cross-linking. Each of these is progressive and increases as the cataract worsens. Significant progress has been made in understanding the origin of the factors that underpin the loss of lens transparency. Of these four hallmarks of cataract, it is protein-protein cross-linking that has been the most intransigent, and it is only recently, with the advent of proteomic methodology, that mechanisms are being elucidated. A diverse range of cross-linking processes involving several amino acids have been uncovered. Although other hypotheses for the etiology of cataract have been advanced, it is likely that spontaneous decomposition of the structural proteins of the lens, which do not turn over, is responsible for the age-related changes to the properties of the lens and, ultimately, for cataract. Cataract may represent the first and best characterized of a number of human agerelated diseases where spontaneous protein modification leads to ongoing deterioration and, ultimately, a loss of tissue function.

Connexin Mutants Compromise the Lens Circulation and Cause Cataracts through Biomineralization

“…The biochemical changes present in lenses with cataracts due to different causes have been extensively studied. Abnormalities include the formation of high molecular weight protein aggregates, post-translational modification of lens proteins, protein cleavage, and protein degradation (reviewed in [31][32][33]). Calcium has also been implicated in cataract pathogenesis [34].…”

Effect of a Lens Protein in Low-Temperature Culture of Novel Immortalized Human Lens Epithelial Cells (iHLEC-NY2)

“…The factors that have been reported to affect the prevalence of nuclear cataracts include smoking [ 27 ], temperature [ 4 ], and diet [ 28 ]. A cohort study revealed that smoking was associated with an increased risk of age-related cataracts, especially nuclear cataracts [ 29 ].…”

Antioxidant Defenses in the Human Eye: A Focus on Metallothioneins

“…As previously mentioned, the excess of ROS and subsequent oxidative stress causes damage to DNA, lipids and proteins inhibiting their biological functions [ 179 , 180 , 181 , 182 , 183 ], which affects the eye natural barriers against oxidative damage resulting in the pathogenesis of numerous age-related ocular diseases including cataracts [ 184 , 185 , 186 ], photokeratoconjunctivitis and photokeratitis [ 187 , 188 , 189 , 190 ], dry-eye disorders [ 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 ], diabetic retinopathy [ 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 207 , 208 , 209 ], retinal vascular diseases [ 210 , 211 , 212 ], retinal dystrophies [ 213 ], glaucoma [ 214 , 215 , 216 , 217 , 218 , 219 , 220 , 221 , 222 , 223 ] and AMD [ …”