Proposed Role for Internal Lens Pressure as an Initiator of Age-Related Lens Protein Aggregation Diseases

Abstract

The process that initiates lens stiffness evident in age-related lens protein aggregation diseases is thought to be mainly the result of oxidation. While oxidation is a major contributor, the exposure of lens proteins to physical stress over time increases susceptibility of lens proteins to oxidative damage, and this is believed to play a significant role in initiating these diseases. Accordingly, an overview of key physical stressors and molecular factors known to be implicated in the development of age-related lens protein aggregation diseases is presented, paying particular attention to the consequence of persistent increase in internal lens pressure.

Keywords: cataract; lens; oxidation; presbyopia; protein aggregation.

Figure 1

Schematic representation highlighting the role stressors play on the lens: over time, certain stressors initiate protein misfolding leading to dysfunctional proteins and the disease state.

Figure 2

Representation of an accommodated and unaccommodated lens. Bottom figure – accommodated lens with most water molecules existing in the bound state. Top figure – unaccommodated lens fixed in its compressed configuration trapping free water within interstitium resulting in higher internal pressure.