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EW NEWS & OPINION December 2016 27 by Liz Hillman EyeWorld Staff Writer Currently, OMMP is treated with systemic immunosupressives. 1 Dr. Dart said these types of drugs will control inflammation in 90% of cases. But in some patients, even with inflammation controlled, scar- ring still occurs, and this is what Dr. Dart and his team sought to investi- gate further. The study by Ahadome et al. described research that found evi- dence that aldehyde dehydrogenase family 1 (ALDH1) is upregulated in the scar-making cells (fibroblasts) of OMMP in vivo and in a mouse model, as well as in whole OMMP conjunctival tissue from human donors. 2 They then found that inhibiting ALDH with disulfiram, a drug used to treat alcoholism, could reverse and prevent scarring in the mouse model and restore normal functionality to fibroblast cells in vitro. To reach these conclusions, Dr. Dart said they first started compar- ing proteins expressed in inflamed OMMP tissue to control tissue. They then conducted gene expression analysis in fibroblast cells. "We were only interested in the genes over or under expressed in both the fibroblasts and in the whole tissue. There were only 13; it Eye Hospital, University College London, and Duke University, Durham, North Carolina, however, not only described a potential mech- anism leading to scarring in ocular mucous membrane pemphigoid (OMMP), but identified an already licensed medication that could lead to reversal of scarring and prevent it from progressing. "Every eye department will have a few [mucous membrane pemphi- goid] patients; I have 150 [patients] because we're interested in the problem," Dr. Dart said, adding that while the prevalence of the disease is low in the general population, ophthalmologists could be interest- ed in this study's findings because MMP is "one of the most difficult external diseases that any of us have to manage." The research According to the National Organi- zation for Rare Disorders, MMP is characterized by lesions affecting mucous membranes of the body. These include the nose, throat, genitalia, and anus, but the eyes and mouth are the most commonly af- fected orifices. The scarring of these lesions, if severe, can affect organ function. Researchers identify possible therapy to treat ocular cicatricial pemphigoid scarring W hile trachoma might be the leading infec- tious cause of scar- ring-related blindness worldwide, it's largely confined to developing countries. Conversely, the most common cause of immune-mediated scarring conjunctival disease in developed countries is mucous membrane pemphigoid (MMP). Though rare, about 20% of those whose eyes are affected by MMP—also called ocular cicatricial pemphigoid—will become blind in both eyes, and 30% will become blind in one eye, said John Dart, MD, consultant ophthalmologist, Moorfields Eye Hospital, London, and honorary professor, University College London. "We've never had a mecha- nism, we never understood why the scarring occurs [in these patients], and there are no treatments for scar- ring," Dr. Dart said. New research published by Dr. Dart and colleagues at Moorfields Drug used for alcohol addiction found to have application in ocular scarring disease was a tiny number," Dr. Dart said. "Of those, only three were likely going to be relevant to scarring. We knew when we got ALDH that it might be relevant." Dr. Dart said they first inhibited ALDH with diethylaminobenzalde- hyde (DEAB) in the lab and then realized that disulfiram was already commercially available. Repeating the studies with the latter drug, he said they found "it worked a treat." "What's more, when we took retinoic acid—the metabolite of ALDH—and fed that to control cells … we found we could make the fibroblasts abnormal in all the assays," Dr. Dart said. After conducting these studies in vitro, Sarah Ahadome, PhD, at the time a post-doctoral student in the lab of Daniel Saban, PhD, at Duke University, observed mice in the lab with severe inflammatory eye disease, which was found to mimic OMMP. "She thought she would see if [the mice] happened to scar because the inflammation looked just as bad as what we get in pemphigoid, and low and behold, the mouse scarred. We have never had [an animal] Recent research has found a possible treatment for scarring caused by ocular mucous membrane pemphigoid—an already licensed drug used for alcohol addiction. Source: John Dart, MD continued on page 28

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