Edwards R B, Adler A J, Dev S, Claycomb R C
Department of Ophthalmology, Boston University School of Medicine, MA 02118.
Exp Eye Res. 1992 Apr;54(4):481-90. doi: 10.1016/0014-4835(92)90126-d.
Previous observations have shown that Müller glial cells of the vertebrate retina contain cellular retinoid-binding proteins, that the retina contains retinoic acid, and that cellular retinoic acid-binding protein is present in amacrine neurons (and, in some species, Müller cells) within the retina. These findings led to the suggestion that Müller cells may synthesize retinoic acid and release it for use by other retinal cells. To test this possibility, we cultured Müller cells from adult rabbit retinas, incubated the cultures with radioactive retinol, and identified and quantified the resultant radioactive retinoids by HPLC. Retinaldehyde was rapidly synthesized from retinol, reaching a plateau of 1-2 pmol mg-1 cell protein by 30 min. Retinoic acid initially accumulated more slowly, but by 30 min constituted most of the synthesized retinoid. While the retinaldehyde remained within the cells, retinoic acid was rapidly released into the medium; extracellular retinoic acid exceeded the intracellular amount after 30 min of incubation. Smaller amounts of retinyl esters were also synthesized and retained by the cells. These results are consistent with the suggestion that Müller glia are a source of retinoic acid in the retina. The synthesis of retinoic acid by these cells, and the presence of retinal neurons that contain cellular retinoic acid-binding protein, raise the possibility that retinoic acid plays a role in the retina, although this role is not presently known. Furthermore, these results may have implications for other parts of the adult nervous system. Adult brain contains retinol- and retinoic acid-binding proteins, and, therefore, may also be a site of retinoic acid metabolism. Because of the relatively simple cellular organization of the retina and its demonstrated capacity to synthesize retinoic acid, the retina may be a system of choice for further studies of the synthesis and function of retinoic acid in adult neural tissue.
先前的观察结果表明，脊椎动物视网膜的穆勒胶质细胞含有细胞视黄醇结合蛋白，视网膜含有视黄酸，并且细胞视黄酸结合蛋白存在于视网膜内的无长突神经元（以及某些物种的穆勒细胞）中。这些发现提示，穆勒细胞可能合成视黄酸并释放出来供其他视网膜细胞使用。为了验证这种可能性，我们培养了成年兔视网膜的穆勒细胞，用放射性视黄醇孵育培养物，并通过高效液相色谱法鉴定和定量产生的放射性类视黄醇。视黄醛迅速从视黄醇合成，到30分钟时达到1 - 2 pmol mg-1细胞蛋白的平台期。视黄酸最初积累较慢，但到30分钟时构成了大部分合成的类视黄醇。视黄醛保留在细胞内，而视黄酸迅速释放到培养基中；孵育30分钟后，细胞外视黄酸超过了细胞内的量。细胞还合成并保留了少量的视黄酯。这些结果与穆勒胶质细胞是视网膜视黄酸来源的观点一致。这些细胞对视黄酸的合成，以及含有细胞视黄酸结合蛋白的视网膜神经元的存在，增加了视黄酸在视网膜中发挥作用的可能性，尽管目前尚不清楚这种作用是什么。此外，这些结果可能对成年神经系统的其他部分也有影响。成年大脑含有视黄醇和视黄酸结合蛋白，因此也可能是视黄酸代谢的场所。由于视网膜的细胞组织相对简单，且已证明其具有合成视黄酸的能力，视网膜可能是进一步研究成年神经组织中视黄酸合成和功能的理想系统。
