Dwork A J, Cavallaro T, Martone R L, Goodman D S, Schon E A, Herbert J
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York.
Invest Ophthalmol Vis Sci. 1990 Mar 1;31(3):489-96.
We reported previously synthesis of transthyretin (TTR), or prealbumin, a transport protein for thyroxine and retinol, in the eyes of rats and cows and showed that in the rat eye, TTR mRNA is localized exclusively in the retinal pigment epithelium (RPE). We now demonstrate by immunohistochemistry that TTR has a more widespread distribution in the rat eye than does its mRNA. Intense immunoreactivity for TTR was found in the RPE, ciliary epithelium, iris epithelium, corneal endothelium, optic nerve fiber layer of the retina, and lens capsule. Depending on the method of processing, immunoreactivity of varying intensity was found also in other ocular structures. In particular, the retinal ganglion cells were strongly immunoreactive on frozen sections but not on paraffin sections. Although vitreous humor was not included in the sections of adult rat eye, sections of a 25-mm rat embryo showed intense immunoreactivity in the vitreous humor. Since plasma TTR does not cross Bruch's membrane into the retina, our findings suggest that ocular TTR is synthesized, at least in part, in the RPE and is transported to specific locations within the eye. Although the physiologic role of ocular TTR is unknown, it is possible that it participates in retinol cycling within the eye. The widespread ocular distribution of TTR may account for the occurrence of various forms of ocular amyloidosis in the familial amyloidotic polyneuropathies, a group of dominantly inherited disorders caused by point mutations in the TTR gene.
我们先前报道了在大鼠和牛的眼中合成甲状腺素运载蛋白（TTR），即前白蛋白，它是甲状腺素和视黄醇的一种转运蛋白，并表明在大鼠眼中，TTR mRNA仅定位于视网膜色素上皮（RPE）。我们现在通过免疫组织化学证明，TTR在大鼠眼中的分布比其mRNA更广泛。在RPE、睫状体上皮、虹膜上皮、角膜内皮、视网膜的视神经纤维层和晶状体囊膜中发现了对TTR的强烈免疫反应性。根据处理方法的不同，在其他眼结构中也发现了强度不同的免疫反应性。特别是，视网膜神经节细胞在冰冻切片上有强烈的免疫反应性，但在石蜡切片上则没有。虽然成年大鼠眼的切片中未包括玻璃体液，但25毫米大鼠胚胎的切片显示玻璃体液中有强烈的免疫反应性。由于血浆TTR不会穿过布鲁赫膜进入视网膜，我们的研究结果表明，眼内TTR至少部分是在RPE中合成的，并被转运到眼内的特定位置。虽然眼内TTR的生理作用尚不清楚，但它有可能参与眼内的视黄醇循环。TTR在眼内的广泛分布可能解释了家族性淀粉样多神经病中各种形式的眼淀粉样变性的发生，这是一组由TTR基因突变引起的显性遗传性疾病。
