Eyeworld

EW RETINA 54 February 2019 Research highlight by Maxine Lipner EyeWorld Senior Contributing Writer Some have also been looking into tissue engineering approaches. "That means that we would make an actual tissue-like structure where donor cells would already have con- tact with each other," Dr. Baranov said. "They would already have a proper architecture." With this type of approach, the delivery becomes more complicated since this is now real graft surgery, he explained; however, once you deliver those cells, since they already have proper tissue architecture, they already have context, making it easier for them to acquire proper function. Dr. Baranov cited a trial led by Peter Coffey, PhD, on delivering retinal pigment epithelium (RPE) as a patch of cells. "We'll see how it's going to develop, but I think it's a great example that it's possible and that we could achieve good results," Dr. Baranov said. With this approach, investigators were able to successfully deliver an RPE patch in two patients, which resulted in an improvement in best corrected visual acuity of up to 29 letters. 2 Still, there are no side-by-side clinical studies showing that a tissue-like patch works better than a suspension of cells, Dr. Baranov stressed. Reprogramming Muller glial cells Bo Chen, PhD, associate professor, Icahn School of Medicine at Mount Sinai, New York, has been working on another strategy: attempting to activate the regenerative capability of the retina using Muller glial cells. In lower species such as zebra fish, Muller glial cells serve as stem cells in residence in addition to support- ing retinal function, Dr. Chen ex- plained. "Whenever there's a loss of retinal neurons by injury or damage, these cells immediately move into the regenerative state and divide and make more retinal neurons," he said, adding that unfortunately, Muller glial cells do not perform this regenerative function in mammals. Dr. Chen and fellow investiga- tors have been working to wake up the regenerative capacity of such cells. "Previous studies show Muller glial cells can be manipulated to have some features of retinal stem cells," he said. "But these earlier studies used strategies such as neurotoxin-induced retinal injury to both used cells delivered as suspen- sion," Dr. Baranov said, adding that this suspension was injected into the subretinal space. There is also now a second gen- eration strategy using pluripotent or induced pluripotent stem cells taken from other areas such as the skin and coaxed back into the embryonic state, then getting them to differen- tiate into retinal pigment epithelium cells or neurons. "This is a challenge because it's hard to make something in vitro that would be the same as in vivo," he said. He noted that with any of these approaches, a lot of cells die during the injection and some do not properly integrate into the retina, instead remaining in the intermediate space. approaches to handling the fact that cells on the human retina do not regenerate on their own. The goal is to find a way to properly replace lost cells. "We want to make a cell that would mimic a retinal cell as closely as possible," Dr. Baranov said. "Then we would deliver it into a recipient environ- ment, and the cell that we would deliver would integrate properly and become a real cell." Techniques One approach deals with taking retinal progenitor cells and expand- ing them in incubators. The idea is to then inject the cells back into the eye and have them function, Dr. Baranov explained. "We found at least two trials [in the literature] and Retinal regeneration making inroads W hen it comes to retinal stem cell regenera- tion for conditions such as age-related macular degeneration and retinitis pigmentosa, a variety of different approaches have been tried, according to Petr Baranov, MD, assistant scientist, Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston. "In terms of transplantation cell replacements, it's interesting how the whole field has been developing for the last 3 decades," Dr. Baranov said. In a review published in Therapeutic Advances in Ophthalmology, 1 Dr. Baranov took a closer look at current Stem cell status De novo genesis of rod photoreceptors in the eye Source: Bo Chen, PhD

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