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    Regenerative cell therapy, tissue engineering are future treatments

    While ALK, EK have evolved for corneal replacement, researchers seeking new directions


    The difference is that in early Fuchs’ the endothelial disease is localized, and later becomes more widespread. For bullous keratopathy and regrafting, there is widespread endothelial destruction.

    For successful endothelial cell regenerative therapy, the endothelium should be regenerated from cells in the paracentral area of the cornea. By looking at the areas around the central area on specular microscopy you can see what the endothelial cells are like.

    If they are healthy in that area, these are the cells that are going to repopulate the area where guttata are found. This will determine whether or not a patient is appropriate for this approach.

    “Using synthetic guttata we developed3, we are able to track human primary endothelial cells as they go into a guttata field, to get an estimate of how much of a problem guttata will cause in a regenerative cell therapy approach,” explained Jodhbir S. Mehta, PhD, Singapore National Eye Center. “We found that the higher the density of the guttata, the more restriction they have on the speed of the regenerative cells, and the height and shape of the guttata also had an influence.

    “So if you have a high-density guttata field, you should strip this before approaching a regenerative cell therapy concept. Stripping the guttata will leave you with doing a primary descemetorhexis,” Dr. Mehta added.

    “In the literature, there is variability in outcomes of primary descemetorhexis surgery, but the outcomes seem to be slightly better in those younger than 60 year olds,” he said. “We wanted to make this a little bit more predictable, so we took matched pairs of ex vivo corneas, scratched one, and peeled the other.”

    The Singapore researchers added ROCK inhibitor to one donor, but not the other, to look at the effect of age and the effect of ROCK inhibitor.”

    What the researchers found was the endothelial cell migration overwhelmingly does better in the presence of a basement membrane, with or without ROCK inhibitor added.

    The ROCK inhibitor allowed an increase in cellular migration in the older age groups. Thus, the ROCK inhibitor allows this type of regenerative therapy to be done in an older patient.

    “So our concept of regenerative therapy for Fuchs’ dystrophy involves stripping away the guttata with high density and transplanting a pure Descemet’s membrane,” Dr. Mehta said. “The age of the patient will decide whether you need to use a ROCK inhibitor or not.”

    Tissue engineering

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