Wetzel M G, Fahlman C, O'Brien P J, Aguirre G D
Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, Bethesda, MD 20892.
Exp Eye Res. 1990 Jan;50(1):89-97. doi: 10.1016/0014-4835(90)90014-l.
The recessive genetic defect in miniature poodles which results in progressive rod-cone degeneration (prcd) has been investigated in an attempt to determine the biochemical abnormality involved. In the present study, the rod outer segments of young prcd affected miniature poodles and normal dogs have been compared with respect to the incorporation of intravitreally injected [3H]palmitic acid. [14C]linolenic acid, and [14C]docosahexaenoic acid into neutral lipids and phospholipids as well as [3H]palmitate and [14C]leucine into rhodopsin. In addition, 3 mm trephined punches of retinas were incubated with [3H]palmitic acid, [3H]arachidonic acid, [14C]linolenic acid, [3H]serine, [14C]glycerol and [14C]leucine. No difference in incorporation of labeled precursors into lipids or rhodospin was noted between prcd affected and normal retinas. Phosphatidyl choline appeared to function as a carrier of fatty acids to the rod outer segment where they were redistributed to other phospholipids. An interesting lack of conversion of the essential fatty acid linolenic acid to docosahexaenoic acid was noted in both normal and affected retinas. This conversion involves elongation and desaturation of linolenic acid and may take place primarily in extraretinal tissues such as the liver. This finding, in conjunction with a parallel study of plasma fatty acids which has shown significantly lower levels of docosahexaenoic acid in prcd affected poodles, points to a possible systemic defect in the metabolism or transport of docosahexaenoic acid, a fatty acid uniquely enriched in the photoreceptor outer segments.
为了确定其中涉及的生化异常，人们对导致迷你贵宾犬进行性视杆-视锥细胞变性（prcd）的隐性遗传缺陷展开了研究。在本研究中，就玻璃体内注射的[3H]棕榈酸、[14C]亚麻酸和[14C]二十二碳六烯酸掺入中性脂质和磷脂的情况，以及[3H]棕榈酸和[14C]亮氨酸掺入视紫红质的情况，对年轻的患prcd的迷你贵宾犬和正常犬的视杆外段进行了比较。此外，将3毫米视网膜环钻切片与[3H]棕榈酸、[3H]花生四烯酸、[14C]亚麻酸、[3H]丝氨酸、[14C]甘油和[14C]亮氨酸一起孵育。在患prcd的视网膜和正常视网膜之间，未发现标记前体掺入脂质或视紫红质方面存在差异。磷脂酰胆碱似乎充当脂肪酸向视杆外段的载体，在视杆外段脂肪酸被重新分布到其他磷脂中。在正常视网膜和患prcd的视网膜中均发现了一个有趣的现象，即必需脂肪酸亚麻酸向二十二碳六烯酸的转化缺乏。这种转化涉及亚麻酸的延长和去饱和，可能主要发生在视网膜外组织如肝脏中。这一发现，连同一项关于血浆脂肪酸的平行研究（该研究表明患prcd的贵宾犬中二十二碳六烯酸水平显著降低），指出了二十二碳六烯酸（一种在光感受器外段独特富集的脂肪酸）在代谢或运输方面可能存在的全身缺陷。
