Evans B L, Smith S B
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912-2000, USA.
Mol Vis. 1997 Oct 24;3:11.
Mice homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene have a retinal degeneration characterized by slow loss of photoreceptor cells and compromised retinal pigment epithelial (RPE) structure and function. The levels of retinyl esters, which are essential for generation of 11-cis-retinaldehyde for the formation of rhodopsin, were reported previously to be elevated by 6 weeks postnatally in the RPE of vitiligo mutant mice. The purpose of the present study was to determine whether this elevation was due to increased activity of lecithin:retinol acyl transferase (LRAT) the enzyme that converts all-trans-retinol to retinyl esters.
Retinoids extracted from the RPE and neural retina of mutant and normal mice ages 2, 4, 6 and 8 weeks were analyzed by reversed-phase HPLC. The esterification capacity of the RPE to convert 3H-retinol to 3H-retinyl ester was determined by HPLC in mutant and normal mice at 3 and 9 weeks.
Retinyl ester levels were elevated significantly in the mutant RPE as early as postnatal week 2 and were four-fold greater by 8 weeks. The esterification assay indicated no significant differences between mutants and controls at 3 weeks. At 9 weeks, the esterification activity of the mutant RPE was significantly reduced compared to controls rather than elevated.
The data suggest that the accumulation of retinyl esters is not due to increased LRAT activity. Alternative explanations for the retinyl ester accumulation are discussed.
小眼畸形（Mitf）基因白癜风突变的纯合子小鼠存在视网膜变性，其特征为光感受器细胞缓慢丧失以及视网膜色素上皮（RPE）结构和功能受损。视黄酯水平对于生成用于视紫红质形成的11 - 顺式视黄醛至关重要，先前报道在白癜风突变小鼠的RPE中，出生后6周视黄酯水平升高。本研究的目的是确定这种升高是否归因于卵磷脂：视黄醇酰基转移酶（LRAT）活性增加，该酶可将全反式视黄醇转化为视黄酯。
通过反相高效液相色谱法分析2、4、6和8周龄突变小鼠和正常小鼠的RPE及神经视网膜中提取的类视黄醇。在3周和9周时，通过高效液相色谱法测定突变小鼠和正常小鼠RPE将3H - 视黄醇转化为3H - 视黄酯的酯化能力。
早在出生后第2周，突变小鼠RPE中的视黄酯水平就显著升高，到8周时增加了四倍。酯化试验表明，在3周时突变体与对照之间无显著差异。在9周时，与对照相比，突变小鼠RPE的酯化活性显著降低而非升高。
数据表明视黄酯的积累并非由于LRAT活性增加。文中讨论了视黄酯积累的其他解释。
