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39 EW CORNEA January 2017 HGF may also work in concert with laser refractive surgery to curtail haze. While this has not yet been tested, models indicate that this could be the case. If this proves true, an HGF-containing medication could be used following laser re- fractive surgery. "It can prevent the development of corneal haze after laser refractive surgery, which stays for months," he said. There is still much to be learned about how HGF might be admin- istered clinically. In the published study, it was applied as an eye drop twice a day for 7 days post injury, but investigators are still determin- ing what the ideal regimen may be. "All of these experiments are still underway, and we are also looking for some additional function of HGF on corneal epithelial cells, as well as how HGF regulates the inflamma- tion," Dr. Chauhan said. With the stem cells, faster corneal epithelial healing has been seen. This makes investigators think that the HGF is also promoting epithelial growth. Dr. Chauhan hopes that the study will help practitioners rec- ognize that HGF has the potential to get converted into a therapy for corneal injury that will allow for the prevention of opacity, as well as for the promotion of transparency. Going forward, more inves- tigations are necessary. "We need further studies on the direct effect of HGF on epithelial cells and inflammation," Dr. Chauhan said. In addition, investigators plan to compare efficacy of HGF to current treatments. EW Reference 1. Mittal SK, et al. Restoration of corneal transparency by mesenchymal stem cells. Stem Cell Reports. 2016;7:583–590. Editors' note: Dr. Chauhan has no financial interests related to his comments. Contact information Chauhan: Sunil_Chauhan@MEEI.HARVARD.EDU by Maxine Lipner EyeWorld Senior Contributing Writer for the stem cell therapy, we now have a factor and can go for that," Dr. Chauhan said. The thinking is that in the inflamed cornea, the HGF prevents the basic mechanism of fibrosis. It inhibits the conversion of fibroblast into myofibroblast, which if unchecked results in fibro- sis and opacity of the cornea, he explained. Applying HGF From a clinical perspective, Dr. Chauhan views this as a boon since this HGF molecule is well defined. By contrast, due to manipulations, you never know just what you are getting with stem cells, he pointed out. "This molecule is well defined pharmacologically," he said. "We can characterize its pharmacokinet- ics for topical application as an eye drop." When dealing with just the factor, with many of the hurdles to working with stem cells removed, there is an ease to administration, Dr. Chauhan continued, adding that in the right vehicle this is something that could be handled by patients themselves. He envisions that an HGF-con- taining medication would poten- tially be an effective treatment for corneal injury, either from surgery, chemical burns, or physical trauma, including combat wounds. But these are not the only potential clinical applications. Dr. Chauhan thinks work to promote corneal transpar- ency, Dr. Chauhan noted. "However, in all of those studies they're using the stem cells as a whole to repair the corneal injury," he said. "Since it's tough in the United States to use stem cell therapy, we wanted to know the mechanism." Investigators found that these MSCs were not differentiating into corneal cells during injury and looked deeper into what they were doing. They determined that MSCs were secreting some growth factors that were preventing opacity, Dr. Chauhan explained. "We screened these mesenchymal stem cells for a series of several growth factors and regulatory cytokines and found that stem cells produced maximum levels of hepatocyte growth factor in the inflamed cornea," he said, adding that from there they started charac- terizing the effects. They found that when they silenced the expression of HGF in the stem cells, these stem cells could no longer repair the cor- neal injury and restore transparency. The HGF was critical for the corneal repair in preclinical models, Dr. Chauhan said. It then became a question of whether HGF alone was sufficient to restore transparency. The investiga- tors found this to be the case. This was as effective as the whole stem cell. "It's more relevant for the trans- lational impact. Rather than going New findings may pave the way for pharmaceutical therapies to reverse corneal scarring and potentially allow those who have had injuries to see again I nvestigators have determined how mesenchymal stem cells (MSCs) work to restore clarity to the cornea and have identified the key molecule, dubbed he- patocyte growth factor (HGF), that may be responsible, according to Sunil Chauhan, PhD, Schepens Eye Research Institute of Massachusetts Eye and Ear, and assistant professor of ophthalmology, Harvard Medical School, Boston. Dr. Chauhan and colleagues reported on the research in Stem Cell Reports. 1 While prior research has shown promise for mesenchymal stem cells, investigating these in the U.S. can be problematic, Dr. Chauhan pointed out. "The stem cell itself is good, but stem cell therapy, at least in the U.S., is very tightly regulated," he said, adding that it's not easy for clinics to use these. Mechanism identified Investigators decided to take a closer look at how the stem cells might be operating. There are several scien- tists worldwide looking at how MSCs Growth factor for restoring corneal transparency identified Research highlight Bright field images showing normal transparent cornea (left), which, post-traumatic injury, develops opacity (scarred cornea, right) and leads to visual degradation or even blindness Source: Sunil Chauhan, PhD

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