Biophysical chemistry of the ageing eye lens

Abstract

This review examines both recent and historical literature related to the biophysical chemistry of the proteins in the ageing eye, with a particular focus on cataract development. The lens is a vital component of the eye, acting as an optical focusing device to form clear images on the retina. The lens maintains the necessary high transparency and refractive index by expressing crystallin proteins in high concentration and eliminating all large cellular structures that may cause light scattering. This has the consequence of eliminating lens fibre cell metabolism and results in mature lens fibre cells having no mechanism for protein expression and a complete absence of protein recycling or turnover. As a result, the crystallins are some of the oldest proteins in the human body. Lack of protein repair or recycling means the lens tends to accumulate damage with age in the form of protein posttranslational modifications. The crystallins can be subject to a wide range of age-related changes, including isomerisation, deamidation and racemisation. Many of these modification are highly correlated with cataract formation and represent a biochemical mechanism for age-related blindness.

Functional Amyloid Protection in the Eye Lens: Retention of α-Crystallin Molecular Chaperone Activity after Modification into Amyloid Fibrils

“…The lens is a unique organ; it continues to grow throughout life yet lacks a blood supply and exhibits no protein turnover. As such, the crystallin proteins in its centre are as old as the individual [ 1 , 2 ]. To maintain lens transparency and the high refractive index necessary for vision, the crystallins must remain stable and in solution.…”

“…The crystallin proteins are primarily found within the mammalian eye lens where they form part of the protein array that focuses light onto the retina via a supramolecular, liquid-like order [ 1 , 2 , 3 ]. Crystallins are highly stable proteins, as there is very limited protein turnover in the lens, particularly in its centre [ 4 , 5 ].…”

Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts

“…It lacks blood vessels that can scatter and absorb light as well as light scattering cellular organelles such as nuclei, mitochondria, and endoplasmic reticula that are removed during differentiation of the epithelial into fiber cells. Light scattering is further minimized by the specialized organization and composition of the tightly packed fiber cells which contain structural crystallin proteins that also assist in maintaining the proper refractive index in the lens 8,9 . Since the lens fiber cells lack the capacity for protein turnover and repair, specific antioxidant defenses and protein chaperones are present within these fiber cells to protect lens proteins from post-translational changes and aggregation 8,10–13 .…”

Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed βH-Crystallins Polymerization in Calcium-Induced Experimental Cataract

“…Crystallins possess a high degree of packing regularity, leading to optical properties responsible for lens transparency. Changes in the crystalline structure, degradation, and other chemical modifications lead to the insolubilization and aggregation of these proteins resulting in cataract [ 5 ], which represents the major cause of blindness worldwide. In particular, it is well established that in some cases the lens opacification process may depend on post-translational modification in various proteins, including crystallins [ 6 ].…”