摘要
长链3-羟酰-辅酶A脱氢酶(LCHAD)缺乏的视网膜病早期就会对视网膜色素上皮细胞(RPE)和脉络膜血管层产生一定的影响。RPE在活体上的培养需要线粒体内对脂肪酸的β-氧化。为了进一步说明LCHAD视网膜病的发病机制,笔者用β-氧化酶抗体对人类眼和大脑进行了免疫组织化学反应分析。
The retinal pigment epithelium (RPE) and the choriocap-illaris are affected early in the retinopathy associated with long-chain 3 - hydroxyacyl-CoA dehydrogenase (LCHAD) de-ficiency. RPE in culture possesses the machinery needed for mitochondrial fatty acid β-oxidation in vitro. To further elucidate pathogenesis of LCHAD retinopathy, we performed immunohistochemistry of the human eye and brain with antibodies to β-oxidation enzymes. Human eye and brain sections were stained with antibodies to medium-chain (MCAD) - and very long-chain acyl-CoA dehydrogenase (VLCAD), short-chain 3 - hydroxyacyl-CoA dehy-dro-genase (SCHAD), and mitochondrial trifunctional protein (MTP) harboring LCHAD. Antibodies to 2 -methyl -3 -hydroxybutyryl-CoA dehydrogenase (MHBD) and cytochrome c oxidase subunit I (COXI)were used as a reference. VLCAD, MTP, MCAD, SCHAD, MHBD, and COX I antibodies labeled most retinal layers and tissues of the human eye actively involved in oxidative metabolism (extraocular and intraocular muscle, the RPE, the corneal endothelium, and the ciliary epithelium). MTP and COX I antibodies labeled the inner segments of photoreceptors. The choriocapillaris was labeled only with SCHAD and MCAD antibodies. In the brain, the choroid plexus and nuclei of the brain stem were most intensely labeled with 3 - oxidation antibodies, whereas COX I antibodies strongly labeled neurons in several regions of the brain. Mitochondria! fatty acid β - oxidation likely plays a role in ocular energy production in vivo. The RPE rather than the choriocapillaris could be the critical affected cell layer in LCHAD retinopathy. Reduced energy generation in the choroid plexus may contribute to the cerebral edema observed in patients with (3 - oxidation defects.
