A Look At A Protein Essential For The Normal Structure Of The Eye Lens

Klotho is a gene that has been implicated in the control of aging in mammals. It belongs to a small family of related genes, one of which, KLPH (or Lctl), turns out to have strongly preferred expression in the eye lens.

Age-related problems in the lens, such as cataracts and the gradual loss of accommodation and increased focusing defects, are major contributors to vision loss worldwide. Indeed, deletion of the KLPH gene in mice led to age-related focus problems. However, this is not a simple age issue, it reflects the accumulation of defects in the organization of lens cells from early stages. The lens is built from layers of highly elongated fiber cells. These extend from the equator of the lens all the way round to the poles where they meet up in well-organized sutures. Evidence suggests that this is controlled through the mechanisms of planar cell polarity (PCP) an important process involved in the organization of all epithelial cells and the normal formation and function of the cell cilium. Deletion of KLPH disrupts this neat organization, producing loose and abnormal sutures, reducing both transparency and focusing power.


KLPH is localized to the anterior epithelial layer of the lens. How does it affect fiber cell organization? RNA sequencing of the lens shows that deletion of KLPH leads to the almost complete loss of expression of another gene, Clic5. Clic5 is expressed in many tissues. In the ear, it is essential for the normal function of the sensory cells and mutation leads to deafness. In the lens, it is associated with the cilium/centrosome complex which plays a key role in cytoskeleton organization and intracellular trafficking in most cells. Loss of Clic5 is associated with loss of the fine control of fiber cell extension needed to form a transparent, functional lens. Since all other tissues in the KLPH deficient mice are normal, this suggests, surprisingly, that KLPH is part of a lens-specific mechanism for control of Clic5, presumably tailored for the exquisite organization of lens fiber cells.

This very specific role for KLPH raises the possibility that other, more widely expressed, members of the klotho family may also exert some of their functions through control of the cilium/centrosome complex. It also adds to evidence that the Clic family, originally thought to be intracellular chloride channel proteins, may function as key components of the cilium and in the control of cellular architecture in many cells.

However, it is also possible that KLPH is another example of gene recruitment or the evolutionary co-option of existing proteins for new functions in the lens. During the evolution of the vertebrate lens, existing proteins were recruited to play new structural roles in the lens. These include the crystallins, recruited from heat-shock proteins, enzymes and other families and lengsin, a lens-specific protein essential for normal maturation of lens fiber cells, which belongs to an ancient branch of the glutamine synthetase family but now plays a structural, not enzymatic, role in the lens.

Whatever its wider significance, the role of KLPH in fine-tuning the optical properties of the lens suggests it may be involved in some of the more subtle defects in focus and clarity that affect so many human patients.


These findings are described in the article entitled The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation, recently published in the journal Experimental Eye Research

This work was conducted by Jianguo Fan, Joshua Lerner, M. Keith Wyatt, Phillip Cai, Katherine Peterson, Lijin Dong, and Graeme Wistow from the National Eye Institute, part of the National Institutes of Health.


  1. Fan, J., Lerner, J., Wyatt, K.K., Cai, P, Peterson, K., Dong, L. and Wistow, G. (2018) The Klotho-related protein Klph (Lctl) has preferred expression in lens and is essential for expression of Clic5 and normal lens suture formation. Exp. Eye Res. 169:111-121.
  2. Wyatt, K., Gao, C., Tsai, J.Y., Fariss, R., Ray, S. and Wistow, G. (2008). A Role for Lengsin, a Recruited Enzyme, in Terminal Differentiation in the Vertebrate Lens. J. Biol. Chem. 283:6607-15.



How Chemical Compounds Affect Fruit Bats’ Plant Interactions

Fruit bats are known to be able to discriminate, select, and track the essential oils of their preferred fruits. A […]

Mechanical Isolation: Examples And Definition

Mechanical isolation is a form of reproductive isolation that prevents two different species from interbreeding with one another. Along with […]

Is There A Hereditary Link Between Testicular And Ovarian Cancer?

Our research group at Roswell Park Comprehensive Cancer Center, led by Kirsten Moysich, PhD, MS, is specifically interested in studying […]

Looking Beyond Standard Model Cosmology: Making A Case For Development Of Observational Tools For Alternative Models

A typical galaxy contains billions and trillions of stars, like our closest neighbor, the Sun. In the field of Cosmology, […]

Exaggerated Weapons In New Zealand Spiders – Does Size Matter? 

We have always been thrilled by animal weapons. From enormous antlers to fangs to crab claws, in their multitude of […]

Map Of Every Florida Beach

Looking at a map of Florida beaches makes you realize just how beautiful Florida’s coastline is. From the famous South […]

Where Does Glycolysis Take Place In A Cell?

Glycolysis takes place in the cytoplasm of a cell as the first step in cellular respiration of the Kreb’s cycle. […]

Science Trends is a popular source of science news and education around the world. We cover everything from solar power cell technology to climate change to cancer research. We help hundreds of thousands of people every month learn about the world we live in and the latest scientific breakthroughs. Want to know more?