New appproaches in retinal degeneration treatments

“There’s no doubt that we’re getting there,” said Dr. Robert MacLaren, FRCOphth, of the promise of photoreceptor transplantation for the treatment of end-stage inherited retinal degenerations such as retinitis pigmentosa. Speaking during the Regenerative Medicine & Gene Therapy main session at the 14th EURETINA Congress, Dr. MacLaren described the technical challenge of transplanting photoreceptors into a subretinal space devoid of host photoreceptors.
Several years ago, the question was, “What happens when you inject cells into the subretinal space? Do they migrate into the correct location? Of course, photoreceptors have no mechanism of movement into the retina itself.”
The transplanted cells must maintain a capacity to reconnect with the retina and resture visual function to the host inner retinal layers. “If they come into contact with photoreceptor cells in the outer nuclear layer, a fusion might take place, although we have to be aware of artefacts, as we’re not expecting to see perfectly-formed, transplanted photoreceptors.”
The potential for experimental artefacts was eliminated by transplanting red fluorescent markers into a green fluorescent retina, allowing the distinction between transplanted and host cells. Dr. MacLaren then described a new approach. Using bacteriophages to cut bacterial DNA with Cre recombinase, in the so-called Cre-lox fusion experiment, a transgenic mouse can then express the Cre recombinase. Cre can be used to regulate gene expression. This led to the ex-vivo delivery of the rhodopsin gene to rod precursors using DNA minicircles, which can then be transplanted back into the degenerate rho-/- gene.
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