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Ziqiang Guan, Yiwen Li, Byron L Lam, Rong Wen; Significant age-related accumulation and shortening of dolichol in the normal retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):800.
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Aging is a major risk factor for many of the leading causes of vision loss including age-related macular degeneration (AMD). We investigated age-related changes in lipid metabolism in a retinal lipidomic study. The present work focuses on age-related changes in dolichol contents and dolichol length distribution in the normal mouse retina. Present in all cellular membranes, dolichols are alpha-saturated polyisoprenoid alcohols containing 16-22 isoprene units in human cells.
C57/B6 wild-type mice of different ages ranging from P1 (postnatal day 1) to 12m (month) were utilized. Lipids were extracted from retinas using a modified Bligh-Dyer method. Dolichols were measured by reverse phase liquid chromatography/mass spectrometry (LC/MS) using a 4000 QTRAP mass spectrometer (AB-Sciex). For comparison, dolichol contents were normalized with the amount of PC (phosphatidylcholine) in each sample.
We measured 5 major dolichol species, including dolichol-16, -17, -18, -19, and -20 (representing numbers of isoprene unit). All species underwent a significant age-related increase in the retina. At P15, the level of dolichol-18, the most abundant dolichol species in mouse, was five times the P1 level. The levels increased 8, 18, and 59 times at 1m, 6m, and 12m, respectively, compared to the P1 level. In addition, we noticed an age-related progressive shortening of dolichol length distribution as described by the ratio of dolichol-18 (D18) vs dolichol-19 (D19). The D18/D19 ratio was 1.1 at 1m and increased steadily to 1.6 at 6m and 1.9 at 12m.<br />
Our study discovered dramatic age-related changes in dolichol in the retina. The age-related accumulation of dolichols and the shortening of dolichol length distribution could be used as quantifiable biomarkers for retinal aging.<br />
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