Eyeworld

EW RETINA 64 June 2015 Investigators are also working with their counterparts in Israel to see if they have more patients with RP who can be identified using this simple biochemical urine test, Dr. Wen said. EW Editors' note: Dr. Wen has no financial interests related to this article. Contact information Wen: rwen@med.miami.edu by Maxine Lipner EyeWorld Senior Contributing Writer extended beyond that, it might become moot, as the patient's life would likely end before he or she would lose vision. For now, because RP is an orphan disease, investigators plan to provide free testing services and continue to delve into it. "We plan to do a survey, mostly in the Jewish population with a family history of eye problems," he said. "We want to test to see how many people have this problem." dolichol 18 versus dolichol 19 is around 0.47 in urine. In those with RP, however, that changes to 4.1, and carriers were somewhere in between. The high ratio in patients is because instead of D19 being the major peak, in RP cases, D18 be- comes the major peak. "That means that you can identify the mutation simply by measuring this ratio," Dr. Wen said. Mutations in the DHDDS gene are typically found in patients of Ashkenazi Jewish origin. Ziqiang Guan, PhD, a biochem- ist and associate professor at Duke University who was collaborating on efforts to identify these markers using an analytical tool called mass spectrometry, found that urine sam- ples could be used instead of blood. Byron Lam, MD, an ophthalmolo- gist and professor at Bascom Palmer Eye Institute, who was one of the investigators who discovered this RP-causing DHDDS mutation and was collaborating with Drs. Wen and Guan, started to collect urine sam- ples from normal human individu- als, RP patients, and carriers. They next established what the typical levels were for each. The ease of collection of urine samples for determining a patient's RP status had a ready appeal. This was particularly true for young chil- dren, Dr. Wen said. "With babies, if [there is] a family history, we can collect some urine and tell with confidence whether the patient has this mutation," Dr. Wen said. "If the patient does have the mutation we could have an early detection with- out [taking] blood." Treatment possibilities Although not much can yet be done from a treatment perspective, research is ongoing, he said. "This is a metabolic disease and we think we can subtly manipulate the metabolic pathway," Dr. Wen said. He added that they are working on several ap- proaches to see if they can develop a treatment. "If we do, that would be very important to identify young people before they lose their rods," he said. "We could slow down or stop the degeneration." This would enable them to save the patient's sight or slow down the disease and possibly extend vision for a couple of decades, he noted. The disease is a slowly progress- ing one and if treatment could be Simple detection method found A new, non-invasive way of identifying patients with retinitis pigmento- sa (RP) has been found, according to Rong Wen, MD, PhD, professor of ophthalmol- ogy, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine. This detection method involves collecting a urine sample and measuring the ratio between specific lipids, Dr. Wen explained. RP affects about 1 in 4,000 indi- viduals, he said. It is not a single dis- ease, but rather is caused by differ- ent mutations. "There are more than 60 genes involved, and in each gene there could be several mutations," Dr. Wen said, adding that any one of the mutations in these genes can result in a similar phenotype that fits under the umbrella of RP. Most of the RP disease pro- cess deals with rod degeneration. Resulting issues for patients include problems in dim light and with pe- ripheral vision. In strong light, rods are saturated, Dr. Wen explained. "After Edison invented artificial light, we didn't need that much rod function as modern humans living in urban society," he said, adding that on the other hand, rods still serve some purpose. In cases of rod degeneration, night vision is almost nonexistent and peripheral vision diminishes more and more. "So the patient would have a hard time seeing things at night with dim light and would have a hard time seeing with peripheral vision," he said. Patients eventually end up with just a small degree of central vision. After rod degenera- tion, the cones slowly degenerate as well. Detecting RP The detection method for RP in- volves looking for mutations in the dehydrodolichol diphosphate syn- thase (DHDDS) gene, which codes for an enzyme, Dr. Wen explained. "The DHDDS enzyme makes a group of lipids called dolichols," he said. These lipid chains vary in length, with normal humans having a certain amount of dolichol 17, 18, 19, 20, and 21 subunit chains. In normal humans the ratio for Testing for DHDDS retinitis pigmentosa Urinary dolichol profile of a normal individual and a patient with DHDDS recessive retinitis pigmentosa. Dolichol 18 is the dominant species in the patient with a mutation in the DHDDS gene that affects dolichol biosynthesis. Retinal photograph of a patient with DHDDS mutation showing diffuse retinal pigmentary degeneration Source: Rong Wen, MD, PhD

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