November 21, 2001

Cells From The Iris May Replace Retinal Photoreceptors

Posted in: Research and Developments

by Dan Roberts
November 2001

An online publication of the December 2001 publication of Nature Neuroscience has reported that, with genetic manipulation, cells from the iris may be able to replace photoreceptor cells in the retina.

In recent experiments, Dr. Masatoshi Haruta of Kyoto University and colleagues took iris cells from rat eyes, then introduced a gene called Crx that is normally expressed in the photoreceptors. The procedure caused the iris cells to express rhodopsin, a substance in the retina that adapts the eye to changes in light.

According to Haruta, it might be possible to remove some iris tissue, coax the cells into taking on retinal qualities, then transplant them back into the patient’s eye.

The researchers conclude that the preliminary study raises “the possibility that [iris] cells constitute a potential source of retinal transplantation in patients with retinal degenerative diseases or damaged retinas.”

Following are comments on the study by Tom Hoglund, Information Officer for the Foundation Fighting Blindness:

There is a large effort to genetically manipulate cells to offer therapeutic outcomes. For example, Neurotech and The Foundation are working to develop an implantable drug delivery device that contains cells genetically altered to produce large amounts of various survival factors. In animal models, cells transfected with the gene that produces ciliary neurotrophic factor (CNTF) slowed vision loss. This kind of genetic manipulation–adding a single gene or increasing the expression of a certain gene–is a bit further along than the effort to turn an iris cell into a photoreceptor cell.

Over the last few years, researchers have been examining iris cells as possible replacements for retinal pigment epithelial (RPE) cells. RPE cells support photoreceptor cell function by shuttling nutrients, oxygen and various survival factors to the photoreceptor cell layer. Iris cells have some but not all of the same biological capabilities as RPE cells. It could be that when transplanted into the micro environment of the RPE cell layer, iris cells will take on RPE cell function. Or, researchers may need to catalog all functions of RPE cells; figure out how these biological functions are genetically performed; and then manipulate the iris cell to include any missing genes. Iris cells have been transplanted in the sub retinal space in humans and they seem to survive. However, more work is needed to determine whether they can function.

The effort to turn an iris cell into a neural photoreceptor cell is a bit more complicated. CRX, a gene discovered with funding support by FFB, is but one gene involved in photoreceptor cell function. This study shows that with CRX, the iris cells were able to produce rhodopsin, the visual pigment that begins the process of absorbing light and turning it into an electrical signal. The next steps would include creating the neural circuitry that transmits the electrical signals on to other cells.

Further, If these cells would be used in an autologous transplant setting (where the patient was the donor), then it would have to be clear that the iris cells don’t carry the same genetic defect that the photoreceptor or RPE cells carry. This work is all very promising and the faster researchers can discover a complete genetic picture of the retina, the quicker researchers can perfect gene-based therapies.

Genetic medicine holds so much potential in treating disease.

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