Smith Christopher P, Sharma Sheena, Steinle Jena J
Department of Physiology, School of Medicine, Southern Illinois University, 1135 Lincoln Drive, LS III Room 2071, Carbondale, IL 62901, USA.
Exp Eye Res. 2007 Jan;84(1):75-81. doi: 10.1016/j.exer.2006.08.018. Epub 2006 Oct 30.
While age-related night vision loss and age-related macular degeneration are well characterized, less is known about the normal aging process in the retina and choroid. The purpose of this study was to ascertain whether dopamine beta-hydroxylase (DBH), beta1- and beta2-adrenergic receptor gene and protein expression are altered in the retina and choroid with age. The retina and choroid were dissected from F344xBNF1 hybrid rats aged 8, 22, and 32 months. Real-time PCR and Western blot analysis were conducted to determine steady-state mRNA and protein expression. Immunohistochemistry (IHC) was conducted to localize DBH protein expression in the retina. DBH protein expression was substantially decreased with age in the retina, particularly in the outer nuclear layer, with no changes in DBH expression noted in the choroid. There was a significant increase in beta1-adrenergic receptor protein expression in retinal samples at 22 months, while beta2-adrenergic receptor protein expression was not affected by age. Decreased expression of DBH with age in the retina could lead to reduced production of norepinephrine, potentially resulting in an increase of beta1-adrenergic receptor expression due to denervation supersensitivity. Gene expression for DBH, beta1- and beta2-adrenergic receptors were observed to peak at 22 months and return to baseline levels by 32 months of age in the choroid. Our findings suggest that the retina may be more sensitive to age-related loss of sympathetic neurotransmission than the choroid, which may partially explain normal age-related vision loss in the elderly.
虽然与年龄相关的夜视能力丧失和年龄相关性黄斑变性已得到充分表征,但对于视网膜和脉络膜的正常衰老过程了解较少。本研究的目的是确定多巴胺β-羟化酶(DBH)、β1和β2肾上腺素能受体基因及蛋白表达在视网膜和脉络膜中是否随年龄而改变。从8、22和32月龄的F344xBNF1杂交大鼠中分离出视网膜和脉络膜。进行实时PCR和蛋白质印迹分析以确定稳态mRNA和蛋白表达。进行免疫组织化学(IHC)以定位视网膜中DBH蛋白的表达。视网膜中DBH蛋白表达随年龄显著降低,特别是在外核层,而脉络膜中DBH表达未见变化。22月龄时视网膜样本中β1肾上腺素能受体蛋白表达显著增加,而β2肾上腺素能受体蛋白表达不受年龄影响。视网膜中DBH随年龄表达降低可能导致去甲肾上腺素生成减少,由于去神经超敏反应可能导致β1肾上腺素能受体表达增加。在脉络膜中观察到DBH、β1和β2肾上腺素能受体的基因表达在22月龄时达到峰值,并在32月龄时恢复到基线水平。我们的研究结果表明,视网膜可能比脉络膜对与年龄相关的交感神经传递丧失更敏感,这可能部分解释了老年人正常的与年龄相关的视力丧失。