Löffler K U, Edward D P, Tso M O
Georgiana Dvorak Theobald Ophthalmic Pathology Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago College of Medicine 60612.
Invest Ophthalmol Vis Sci. 1995 Jan;36(1):24-31.
Increased immunoreactivity (IR) of beta-amyloid and the amyloid-associated proteins tau and amyloid precursor protein (APP) in the brain have been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. However, the expression of these proteins has not been investigated in the normal or diseased human retina.
Using immunohistochemical techniques, we examined the distribution and age-related changes of anti-tau-1, anti-tau-2, anti-APP, and anti-beta-amyloid IR in the human retina at various ages (n = 24), in retinitis pigmentosa (RP, n = 6), and in age-related macular degeneration (ARMD, n = 10).
Tau-1 immunoreactivity was intense in the inner retinal layers and did not change with age or in RP. Eyes with ARMD showed less intense staining but exhibited a similar distribution. Tau-2 IR was faint and did not change with age but was mildly increased in the retinal pigment epithelium (RPE) of eyes with RP and in the retina of eyes with ARMD. APP IR was most prominent in the ganglion cell and nerve fiber layer, and it appeared to increase in ganglion cells of older persons and in RPE cells of eyes with RP and ARMD. Beta-amyloid IR was only detected focally in sub-RPE deposits in eyes from older persons.
The proteins investigated in this study are present in the human retina. The staining pattern of tau is different from the brain, but it shows no age-related changes. The increased immunoreactivity of APP in retinal ganglion cells of older eyes and in RPE cells of eyes with RP and ARMD, as well as the patchy staining of beta-amyloid within sub-RPE deposits, might indicate a relationship of these proteins to retinal aging and possibly to retinal degeneration in RP.
大脑中β-淀粉样蛋白以及与淀粉样蛋白相关的蛋白质tau和淀粉样前体蛋白(APP)免疫反应性(IR)的增加与神经退行性疾病如阿尔茨海默病的发病机制有关。然而,这些蛋白质在正常或患病的人类视网膜中的表达尚未得到研究。
我们使用免疫组织化学技术,检查了不同年龄(n = 24)的人类视网膜、视网膜色素变性(RP,n = 6)和年龄相关性黄斑变性(ARMD,n = 10)中抗tau-1、抗tau-2、抗APP和抗β-淀粉样蛋白IR的分布及与年龄相关的变化。
Tau-1免疫反应性在视网膜内层较强,且不随年龄或RP而变化。患有ARMD的眼睛染色较弱,但分布相似。Tau-2 IR较弱,不随年龄变化,但在患有RP的眼睛的视网膜色素上皮(RPE)和患有ARMD的眼睛的视网膜中略有增加。APP IR在神经节细胞和神经纤维层最为突出,并且在老年人的神经节细胞以及患有RP和ARMD的眼睛的RPE细胞中似乎增加。β-淀粉样蛋白IR仅在老年人眼睛的RPE下沉积物中局灶性检测到。
本研究中所研究的蛋白质存在于人类视网膜中。Tau的染色模式与大脑不同,但未显示出与年龄相关的变化。老年眼睛的视网膜神经节细胞以及患有RP和ARMD的眼睛的RPE细胞中APP免疫反应性增加,以及RPE下沉积物中β-淀粉样蛋白的斑片状染色,可能表明这些蛋白质与视网膜衰老以及可能与RP中的视网膜变性有关。