Functions of the intermediate filament cytoskeleton in the eye lens

Intermediate filaments (IFs) are a key component of the cytoskeleton in virtually all vertebrate cells, including those of the lens of the eye.IFs help integrate individual cells into their respective tissues.This Review focuses on the lens-specific IF proteins beaded filament structural proteins 1 and 2 (BFSP1 and BFSP2) and their role in lens physiology and disease.Evidence generated in studies in both mice and humans suggests a critical role for these proteins and their filamentous polymers in establishing the optical properties of the eye lens and in maintaining its transparency.For instance, mutations in both BFSP1 and BFSP2 cause cataract in humans.We also explore the potential role of BFSP1 and BFSP2 in aging processes in the lens. Intermediate filaments: a dynamic filament network essential to cell functionThe cytoskeleton comprises three major filament systems -microfilaments, microtubules, and intermediate filaments (IFs).IFs were first identified in Howard Holtzer's laboratory in 1968 (1) as polymers differing from microfilaments and microtubules in that they are 10 nm in diameter, intermediate in size between microtubules (25 nm) and microfilaments (6 nm).The name "intermediate" stuck to describe this defining characteristic of IFs.They are the most resilient component of the cytoskeleton, which initially focused attention on the structural roles played by these filaments in cells.This focus helped us understand how individual cells are integrated into tissues via their IFs, but now we are beginning to appreciate the role played by IFs in other cellular processes such as signaling (2).The eye lens is an example of a tissue in which precise cell-cell organization (Figures 1 and 2) is critical to its function, which is to refract photons onto the retina and help produce a focused image via accommodation of the lens.As we discuss here, the lens-specific IFs, also known as beaded filaments, contribute to this cellular organization, and their disruption compromises lens function in vision. The eye lens and the visual system of vertebratesAn optically clear visual apparatus is essential for vision.In vertebrates, the components of this apparatus are the cornea (the major refractive surface of the eye), the lens (which focuses the incoming light), the vitreous (a gel-like substance filling the proximal part of the eye), the inner retina, and the photoreceptors of the outer retina.For light to pass along this visual axis undisturbed, highly ordered cellular and tissue structures are required.Any disturbance in normal cell structure and cell-cell relationships will lead to diffraction, absorbance, or reflection of the light, resulting in disturbed or diminished vision.When this occurs in the eye lens, the condition is referred to as cataract Conflict of interest: The authors have declared that no conflict of interest exists.