Determining the role of fluid flow on lens biomechanics

Abstract

The vertebrate crystalline lens is a highly specialized, avascular, and transparent structure whose primary function is to change shape to refract incident light onto the retina. With increasing age, however, the lens undergoes progressive compaction of the fiber cells and crosslinking of the structural proteins, causing it to lose its elasticity. This age-dependent decline in lens ability to change shape is called presbyopia, an ocular condition affecting approximately 2 billion people worldwide. The lens of the eye relies on a specialized microcirculatory system (MCS) to maintain transparency, nutrient supply, and volume homeostasis in the absence of a blood supply. Given that the MCS plays an essential role in volume homeostasis and there is an age-related decline in the function of MCS, modulating the components of the MCS with agonists and antagonists offers a powerful approach to understanding the precise mechanism of presbyopia and identifying novel therapeutic targets for presbyopia. Using chickens, which can deform their lenses to induce shape changes and naturally develop age-related presbyopia, this study investigated the following objectives:

1. To determine the effect of modulators of aquaporin 0 (AQP0) and sodium-potassium ATPase (NKA) pumps on the lens biomechanics. 2. To determine whether TRPV1 and TRPV4 are present in the chicken crystalline lens and how modulating them affects lens biomechanics and protein expression. 3. To determine the temperature-dependent role of the lens microcirculatory system (MCS) in regulating lens biomechanics.

We found that the chicken model is a robust model for investigating lens biomechanical regulation by the MCS. At room temperature, modulating AQP0, water channels altered lens hydrostatic pressure, whereas NKA modulation affected biomechanics only when ionic or volume homeostasis was disturbed. Western blot analysis confirmed the presence of protein expression of both mechanosensitive TRPV1 and TRPV4 channels in chicken lens tissue, mirroring mammalian expression patterns. TRPV4 modulation altered lens biomechanics exclusively at the physiological temperatures, whereas AQP0 and NKA modulation produced no biomechanical effect at the physiological temperature, highlighting temperature-dependent regulation of the lens microcirculatory system.