December 2013

New biomarker for diagnosing patients with degenerative eye disease

retinitis pigmentosa
Fundus of patient with midstage retinitis pigmentosa. Image credit: Christian Hamel, Creative Commons contributor

Retinitis pigmentosa is an inherited eye disease that causes progressive loss of vision, sometimes leading to blindness. In a study published in the December issue of the Journal of Lipid Research, Rong Wen, Byron L. Lam and Ziqiang Guan of the Bascom Palmer Eye Institute at the University of Miami report that patients with retinitis pigmentosa have increased levels of the compound dolichol-18, compared with healthy individuals. Their study suggests that dolichol profiling could be adapted for use in tests to diagnose patients with the disease as well as to identify carriers of the causative gene.
Dolichols are long-chain alcohols containing multiple isoprene units. While the functions of free dolichols are unknown, the enzyme dehydrodolichol diphosphophate synthase, or DHDDS, is known to have paramount importance in the early stages of dolichol synthesis.
The researchers previously discovered a single nucleotide mutation in the gene that encodes DHDDS; this mutation leads to an amino acid change that has been established as the cause of autosomal recessive retinitis pigmentosa in the Ashkenazi Jewish population. The mutation results in abnormal dolichol metabolism.
In this study, urine and plasma samples from retinitis pigmentosa patients and carriers of the gene were analyzed with liquid chromatography-mass spectrometry. In patients, dolichol-18 was found to be the dominant dolichol species, whereas in healthy individuals, the normal dominant dolichol species was dolichol-19.
The researchers assert that their method of examining the ratios of dolichol-18 to dolichol-19 is a more useful measure than traditional genotyping, because it enables the clinician also to observe whether dolichol metabolism has been affected. Abnormal dolichol metabolism is suggested to be related to other neurodegenerative disorders, such as Alzheimer’s disease, so Wen et al.’s finding that dolichol profiling could be useful in evaluating the efficacy of treatments designed to correct such abnormal metabolism shows promising clinical potential.

Mary ChangMary L. Chang ( is publications manager for the Journal of Lipid Research and Molecular & Cellular Proteomics.

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