Breakthroughs

October 2003: FEEDING THE LENS
Bascom Palmer Scientist Discovers Remarkable Lens Structures for Clear Vision

The lens of the eye is a marvel of biological engineering. It has the ability to change shape or “accommodate” in order to focus light, making it possible to see both near and far objects clearly. This is possible because the lens is made up of living cells, which provides for flexibility and elasticity. A problem however, is that most cells are not transparent. To also ensure their crystal clarity, lens cells must sacrifice the tiny light-scattering organelles that give them the ability to feed themselves. It has long been a mystery as to how these cells stay alive and maintain transparency for decades. Bascom Palmer faculty member Valery I. Shestopalov, Ph.D. and collaborator Steven Bassnett, Ph.D. from Washington University School of Medicine have uncovered a remarkable feature of lens structure that provides the supply line for transfer of nutrients and building blocks from the surrounding fluids of the eye. In this new report published in the October 15th issue of the Journal of Cell Science, further features of this pathway are defined.

The ocular lens is composed of cube-shaped cells called “epithelial cells”, which form a monolayer across the surface of the tissue, and elongated “fiber cells”, which constitute the remainder and majority of the tissue volume. Fiber cells are formed continuously throughout life, derived from epithelial cells near the lens equator. Lens growth occurs by the addition of fiber cells to the surface of the tissue. With time, newly differentiated fiber cells bury mature elongated fibers, effectively isolating them from the humors of the eye.

For optical reasons, fiber cells in the lens are tightly packed, and the space between them is narrow and tortuous. Consequently, it is believed that the inner fiber cells do not obtain nutrients directly from the surrounding ocular humors. Rather, small molecules are thought to enter the surface cells and diffuse from cell to cell into the core of the lens. This view of the lens, in which the metabolism of the mature lens fibers is sustained via communication with cells at the periphery, has been termed `metabolic cooperation'.

The lens is richly endowed with channels called “gap junctions” composed of proteins called “connexins”. Gap junction channels allow the passage of small molecules directly from cell to cell. However, Shestopalov and Bassnett showed previously that molecules too large to move through the narrow gap junctional channels can still be transferred from cell to cell.

In this study the researchers followed up on the previous findings by using a novel transgenic model in which scattered lens cells produce a green fluorescent protein (GFP). They found that early in development, GFP expression in scattered fiber cells resulted in a checkerboard fluorescence pattern in the lens. However, at later times, the centrally located fiber cells became uniformly fluorescent, indicating that the protein was passing from cell to cell. In the adult lens, a superficial layer of cells retained the original mosaic fluorescence pattern, but the remainder, and majority, of the tissue was uniformly fluorescent.

The researchers reasoned that a pathway for large molecules must be located at the border between the two distinct labeling patterns. To test this hypothesis, they microinjected a second large fluorescent molecule (dextran) into individual fiber cells and followed its diffusion by time-lapse microscopy. Deep injections resulted in intercellular diffusion of dextran from injected cells. By contrast, when injections were made into superficial fiber cells, the injected cell invariably retained the dextran.

Together, these data provide new evidence that, in addition to being coupled by gap junctions, cells in the lens core are interconnected by a pathway that allows passage of much larger molecules. This special pathway forms during lens and eye development.

Read more…
Click the link above to view the citation and scientific abstract for the above referenced article on the National Library of Medicine’s “PubMed” website. This also provides a link to the complete article published in the Journal of Cell Science.

For this ground-breaking work, Dr. Shestopalov recently received the nation’s most prestigious award for promising young scientists, the Presidential Early Career Awards for Scientists and Engineers (PECASE). For more information, please see the White House press release.

To learn about his current research, please see the Shestopalov Laboratory Page.

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