Abstract
Dolichol is a lipid uniquely important for retinal cells. Mutations affecting dolichol biosynthesis cause non-syndromic retinal degeneration. Aging is a major risk factor for leading causes of vision loss. We characterized age-related changes in dolichol levels in the retinas of C57BL/6 mice of both sexes at the age of PD (postnatal day) 5, 10, 15, 20, 30, 60, 180, 360, and 600 using liquid chromatography-mass spectrometry (LC-MS), a highly sensitive and specific method for dolichol analysis. All four major dolichol species-dolichol-17 (Dol-17), Dol-18, Dol-19, and Dol-20, increased dramatically with age. The largest increase was in Dol-18, which rose by a factor of 100 from PD 5 to PD 600. Age-related dolichol increases occurred in two distinct phases: Phase I (PD 5 to PD 30) and Phase II (PD 30 to PD 600). These phases coincide with the phases of postnatal development and adult aging, respectively. A shift in the dolichol chain-length profile with age was also observed. Dol-19 was the dominant species from PD 5 to PD 15 but Dol-18 became dominant after PD 20. Changes in cholesterol and coenzyme Q9 (CoQ9) followed the same biphasic pattern. The age-related increase in dolichol levels may influence the physical properties of cell membranes, act as an ultraviolet (UV) filter for retinal cells, and serve as a biomarker of retinal aging.