Gouras Peter, Ivert Lena, Landauer Noelle, Mattison Julie A, Ingram Donald K, Neuringer Martha
Department of Ophthalmology, Columbia University, New York, NY, USA.
Graefes Arch Clin Exp Ophthalmol. 2008 Oct;246(10):1395-402. doi: 10.1007/s00417-008-0910-8. Epub 2008 Aug 16.
To compare drusenoid maculopathy in monkeys with human age-related macular degeneration, and evaluate the influence of age, gender and caloric restriction.
Examination by indirect ophthalmoscopy, slit-lamp biomicroscopy and fundus photography, including in some cases fluorescein angiography, was performed on 61 male and 60 female rhesus macaques of ages 10-39 years. Fifty-four of the monkeys were maintained on a calorically restricted diet (approximately 30% lower than control levels) and 67 on an approximately ad libitum diet for 2-19 years, with all other environmental factors held constant. Maculopathies were graded on a 5-point scale and the effects of age, sex, and diet on prevalence and severity were examined. The retinas of six monkeys with macular drusen, 19-28 years old, were examined histologically.
Rhesus monkeys showed a high prevalence (61%) of drusenoid maculopathy. The prevalence and severity of the maculopathy increased with age (p = 0.012). Fully half of all monkeys aged 10-12 years had some detectable degree of drusen. This high prevalence in young adulthood indicates that drusen develop much earlier in rhesus monkeys than in humans, who develop early maculopathy most rapidly at 50-60 years of age, even when correcting for the 3-fold difference in lifespan. No neovascularization or geographic atrophy was found. Females had a higher prevalence and severity than males (p = 0.019). Calorically restricted monkeys had a slightly lower prevalence and severity at 10-12 years than controls, but the difference was not statistically significant. This is an on-going project, and differences between the caloric restricted and ad-lib groups may emerge as the animals age. Some monkeys developed severe maculopathy in their 20s, with others unaffected in their 30s. The histology of drusen resembled those in human retina.
Drusenoid maculopathy is common in rhesus monkeys, even in young adult life. Half of the rhesus monkeys examined have drusen at a much younger age than in humans. Severity of maculopathy was greater in female monkeys, a gender difference not consistently found in humans. No differences were detected due to caloric restriction, but a definitive test of this intervention will require a larger sample, longer period of observation, and/or an earlier institution of caloric restriction. Genetic factors are implied because with similar environments, some monkeys are affected at an early age, while older ones are not.
比较猴类的玻璃膜疣样黄斑病变与人类年龄相关性黄斑变性,并评估年龄、性别和热量限制的影响。
对61只雄性和60只雌性、年龄在10至39岁之间的恒河猴进行间接检眼镜检查、裂隙灯生物显微镜检查和眼底摄影,部分病例还包括荧光素血管造影。54只猴子维持热量限制饮食(比对照水平低约30%),67只猴子维持近似随意饮食,持续2至19年,所有其他环境因素保持恒定。黄斑病变按5分制分级,检查年龄、性别和饮食对患病率和严重程度的影响。对6只年龄在19至28岁、患有黄斑玻璃膜疣的猴子的视网膜进行组织学检查。
恒河猴玻璃膜疣样黄斑病变的患病率很高(61%)。黄斑病变的患病率和严重程度随年龄增加(p = 0.012)。所有10至12岁的猴子中有一半有某种可检测到程度的玻璃膜疣。成年早期的这种高患病率表明,恒河猴玻璃膜疣的出现比人类早得多,人类在50至60岁时黄斑病变发展最快,即使校正寿命3倍的差异也是如此。未发现新生血管或地图样萎缩。雌性的患病率和严重程度高于雄性(p = 0.019)。热量限制的猴子在10至12岁时的患病率和严重程度略低于对照组,但差异无统计学意义。这是一个正在进行的项目,随着动物年龄增长,热量限制组和随意饮食组之间的差异可能会显现出来。一些猴子在20多岁时出现严重的黄斑病变,而另一些猴子在30多岁时未受影响。玻璃膜疣的组织学与人类视网膜相似。
玻璃膜疣样黄斑病变在恒河猴中很常见,即使在成年早期。接受检查的恒河猴中有一半在比人类年轻得多的年龄就有玻璃膜疣。雌性猴子黄斑病变的严重程度更高,这种性别差异在人类中并不一致。未检测到热量限制导致的差异,但对这种干预的明确测试将需要更大的样本、更长的观察期和/或更早开始热量限制。暗示存在遗传因素,因为在相似环境下,一些猴子在幼年时受到影响,而年长的猴子则未受影响。