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Research - Age-related macular degeneration (AMD)

Cell transplantation
   

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It is known that the progression of AMD could be halted if the RPE cells that nursemaid the retina and macula throughout life were to be replaced by fresh healthy cells. In addition, the successful introduction of new cells would lead to the real possibility that many patients would regain some of their lost vision.

In several laboratories throughout the World, including our own, research is going on to grow healthy retinal pigment epithelium (RPE) cells in tissue culture for transplantation and also to develop the transplantation techniques. These investigations have had some success, but there remain some difficulties. After a while, the RPE cells which are donated from a post-mortem eye start to be rejected by the transplant patient. In addition there are problems to solve relating to the delivery of RPE cells into the eye and beneath the macula. Unfortunately short-term success eventually gives way to long-term failure.

Harvesting the transplant patient's own RPE would prevent rejection issues. Unfortunately, this is not a practical proposition. However, we can harvest healthy iris pigment epithelium (IPE) cells from the iris of the transplant patient. A peripheral iridectomy is a minor complication-free procedure that is frequently done during a number of eye operations. It involves removing a small section of the iris at the front of eye.

  • Montage of 2 photos showing the anatomy of a peripheral iridectomy.

    The upper image was obtained using conventional photography and the arrows point to where a small part of the iris has been surgically removed.

    The lower image was obtained by bright-field microscopy and shows a 5 µm section through a piece of iris. The section has been stained with haematoxylin and eosin to highlight the iris architecture. The naturally pigmented IPE monolayer is clearly visible (arrows).
   Montage of 2 photos showing the anatomy of a peripheral iridectomy.

IPE and RPE are embryonically identical cells and as such have many functions in common. Might IPE substitute for RPE in a transplant procedure? If so we will have solved the rejection difficulty at a stroke! The segment of iris would be taken from the fellow eye of the patient and the IPE grown in culture and harvested for transplantation. Clearly we will have to establish how well key RPE biological activities (for macular survival) are conducted by IPE. If we can optimise IPE to perform as well, or nearly as well as RPE, then we will have made an important break through.

We think we have also overcome the difficulty of delivering the RPE cells. Many groups have injected suspensions of cells under the macula and hoped that they will form a monolayer or sheet of functional cells on the natural substrate called Bruch's membrane. Unfortunately they do not! Too often the Bruch's membrane is damaged in the course of the disease and made worse by the micro surgery. We know that the IPE need to be introduced as a sheet of cells before they go into the eye. In addition they need to be on an artificial substrate to replace the damaged Bruch's membrane. The substrates we are developing are thin layers of perforated plastic that can be rolled up like a mini carpet. The roll could then be introduced into the eye, placed under the macula where the diseased tissue has been removed and then flattened out into place while the macula is repositioned.

  • Schematic diagram showing how IPE cells could be transplanted below the macula:

    [A] IPE cells isolated from an iridectomy are cultured on a plastic substrate and rolled into a cylinder prior to surgery.

    [B] The IPE roll is placed by syringe beneath the retina.

    [C] The IPE cylinder is unrolled in place beneath the photoreceptors of the macula and the retina is replaced.
   Schematic diagram showing how IPE cells could be transplanted below the macula.

We have already established techniques to grow RPE and IPE cells in culture, but we still need to further refine them to harvest sufficient iris cells for effective transplant. We have also initiated the process of comparing the biology of RPE and IPE cells. We are also identifying the most appropriate plastic substrate that will allow IPE to form a tight monolayer and undertake key barrier, transport, storage and digestive roles necessary for normal macular function and to prevent blood vessel entry to the retina. The surgical procedures needed for the transplantation have already been developed by our team of surgeons.

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