Michael R
St. Erik's Eye Hospital, Stockholm, Sweden.
Ophthalmic Res. 2000;32 Suppl 1:ii-iii; 1-44.
Several epidemiological investigations show a correlation between cataract development and the dose of ultraviolet radiation (UVR) received. It is experimentally well established that exposure of animal eyes to UVR induces cataract. Most cataracts develop as a gradual increase in lens opacity. Despite this, current estimations of toxicity for cataract are based on the concept that cataract is a binary event. Moreover, current exposure limits for UVR are based on subjective inspections with slit lamp microscopy.
The first purpose of the present study was to determine a statistically defined maximum acceptable dose for ultraviolet radiation-induced cataract based on quantitative data of forward light scattering in lenses. The second purpose was to find possible explanations for light scattering by investigating the morphology and the refractive index distribution in the lens. The third purpose was to describe the development of cataract after UVR on the cellular level.
Six-week-old, female Sprague-Dawley rats received UVR unilaterally in vivo. The radiation from a high pressure mercury lamp was collimated, passed through a water filter and an interference filter or a monochromator (lambdaMAX = 300 nm), and projected onto the cornea. The exposure time was 15 min. The exposure dose ranged between 0.1 and 20 kJ/m2 and the animals were kept between 6 hours and 32 weeks after exposure. The extracted lenses were photographed and forward light scattering was measured. Other methods included light microscopy, fluorescence microscopy, transmission and scanning electron microscopy, freeze-fracture and microradiography.
From a long-term experiment, it was concluded that UVR-exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean forward light scattering remains unchanged between 1 and 32 weeks. Earlier observations, taken together with the current findings, indicate that the optimal time to detect low dose UVR-induced cataract is one week after exposure in rats. The intensity of forward light scattering increases exponentially with increased UVR dose between 0.1 and 14 kJ/m2. Based on this continuous dose-response, a method to determine a maximum acceptable dose to avoid UVR-induced cataract was developed. The statistically defined lower limit of pathologic light scattering is projected on the dose-response function. The dose corresponding to that point can be estimated and was suggested to be called the Maximum Acceptable Dose (MAD). Two low dose UVR exposures with 0 or 6 h intervals between the exposures produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the termination of the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development. Lenses exposed to UVR grow more slowly than their non-exposed contralaterals. This decrease in lens growth was more pronounced with increasing dose. Low doses led to decreased water content in the lens whereas high doses led to swelling. At 6 months after low dose UVR exposure, no global change of the refractive index was found. However, local variations of the refractive index induce a subtle cortical light scattering. In vivo low dose UVR induces programmed cell death which peaks 24 h post-exposure and involves the entire lens epithelium. Dead cells are removed from the epithelium by phagocytosis. This leads to disintegration of the lens epithelium, associated with flake-like opacities at the lens surface. After one week, the epithelium and the equatorial parts of superficial lens fibers contain extracellular spaces. The extracellular spaces together with locally disarranged fibers produce a corrugated opaque lens surface and equatorial opacities. Within several weeks after ex
多项流行病学调查显示白内障的发生与所接受的紫外线辐射（UVR）剂量之间存在关联。实验已充分证实，动物眼睛暴露于UVR会诱发白内障。大多数白内障是随着晶状体混浊逐渐加重而发展的。尽管如此，目前对白内障毒性的评估是基于白内障是一个二元事件的概念。此外，当前UVR的暴露限值是基于裂隙灯显微镜的主观检查。
本研究的首要目的是根据晶状体前向光散射的定量数据，确定紫外线辐射诱发白内障的统计学定义的最大可接受剂量。第二个目的是通过研究晶状体的形态和折射率分布，找到光散射的可能解释。第三个目的是在细胞水平上描述UVR照射后白内障的发展过程。
六周龄雌性Sprague-Dawley大鼠在体内接受单侧UVR照射。高压汞灯发出的辐射经过准直，通过水滤光片和干涉滤光片或单色仪（λMAX = 300 nm），然后投射到角膜上。暴露时间为15分钟。暴露剂量在0.1至20 kJ/m²之间，动物在暴露后6小时至32周内饲养。取出的晶状体进行拍照并测量前向光散射。其他方法包括光学显微镜、荧光显微镜、透射和扫描电子显微镜、冷冻断裂和微放射照相。
从一项长期实验得出，暴露于UVR的晶状体比其对侧晶状体散射更多的光，且较高剂量会诱导更多的光散射。暴露于5 kJ/m²后，在1至32周内平均前向光散射保持不变。早期观察结果与当前发现相结合，表明在大鼠中检测低剂量UVR诱发白内障的最佳时间是暴露后一周。在0.1至14 kJ/m²之间，前向光散射强度随UVR剂量增加呈指数增加。基于这种连续的剂量反应，开发了一种确定避免UVR诱发白内障的最大可接受剂量的方法。将病理学光散射的统计学定义下限投影到剂量反应函数上。可以估计对应于该点的剂量，并建议将其称为最大可接受剂量（MAD）。两次低剂量UVR暴露，暴露间隔为0或6小时，会产生相同程度的晶状体混浊。当第二次暴露在第一次暴露结束后24或48小时进行时，晶状体损伤会增加。暴露后24至48小时内的修复过程似乎对UVR敏感，在此期间的额外暴露可能会加重白内障的发展。暴露于UVR的晶状体比未暴露的对侧晶状体生长更慢。随着剂量增加，这种晶状体生长的减少更为明显。低剂量导致晶状体含水量降低，而高剂量导致肿胀。低剂量UVR暴露6个月后，未发现折射率的整体变化。然而，折射率的局部变化会引起细微的皮质光散射。体内低剂量UVR诱导程序性细胞死亡，在暴露后24小时达到峰值，且涉及整个晶状体上皮。死亡细胞通过吞噬作用从上皮中清除。这导致晶状体上皮解体，与晶状体表面的片状混浊有关。一周后，上皮和晶状体浅层纤维的赤道部分含有细胞外间隙。细胞外间隙与局部排列紊乱的纤维一起产生波纹状不透明的晶状体表面和赤道混浊。在暴露后数周内……
