Aydemir Orhan, Celebi Serdal, Yilmaz Turgut, Yekeler Hayrettin, Kükner A Sahap
Department of Ophthalmology, School of Medicine, Firat Unv Tip Fak Göz Hast AD, Elaziğ, Turkey.
Int Ophthalmol. 2004 Oct-Dec;25(5-6):283-9. doi: 10.1007/s10792-005-2034-z. Epub 2006 Mar 7.
The purpose of this study is to provide evidence that free radical damage is a component of retinal ischemia-reperfusion (I/R) injury, and to determine whether alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) can protect the retina from this injury.
The right eyes of 40 male guinea pigs weighing 500-600 g were used. The animals were randomly assigned to group 1 (control), group 2 (I/R), group 3 (I/R plus alpha-tocopherol), group 4 (I/R plus gamma-tocopherol) and group 5 (I/R plus TPGS). Groups 3, 4 and 5 received four subcutaneous injections at six-hour intervals for total dosage of 800 IU/kg alpha-tocopherol, 1000 IU/kg gamma-tocopherol and 750 IU/kg TPGS, respectively. The first dose of each substance was administered 5 minutes before retinal ischemia. Retinal ischemia was induced for 90 minutes, then followed by reperfusion for 24 hours. Injections of three substances were repeated at 6, 12 and 18 hours during reperfusion. The animals were killed at 24 hours of reperfusion. Sagittal sections of 4 microm were cut and stained with hematoxylin and eosin for light microscopic evaluation. The average thickness (edema) of the inner plexiform layer for each eye was measured in sagittal sections near the optic nerve and expressed in microns.
All the three substances showed statistically significant protection against the formation of retinal edema during ischemia-reperfusion injury. The mean thickness of the inner plexiform layer were 15.0, 25.44, 19.81, 21.38 and 20.88 microm in control, I/R, I/R plus alpha-tocopherol, I/R plus gamma-tocopherol and I/R plus TPGS groups, respectively. The results showed that the thickness of the inner plexiform layer in group 1 (control) was significantly lower than the other groups (p<0.001). The inner plexiform layer was thicker in the I/R group than with I/R plus alpha-tocopherol (p<0.001), I/R plus gamma-tocopherol (p<0.001) and I/R plus TPGS (p<0.01). The inner plexiform layer was not thicker in the I/R plus TPGS group than in the I/R plus alpha-tocopherol and I/R plus gamma-tocopherol groups. Compared to the I/R plus alpha-tocopherol group, the inner plexiform layer was significantly thicker in the I/R plus gamma-tocopherol group (p<0.01).
The results from these experiments indicate that vitamin E forms have protective effects on the retina during retinal ischemia-reperfusion injury, but, the effects of alpha-tocopherol and TPGS appear to be much greater than that of gamma-tocopherol.
本研究旨在提供证据证明自由基损伤是视网膜缺血再灌注（I/R）损伤的一个组成部分，并确定α-生育酚、γ-生育酚和维生素E聚乙二醇1000琥珀酸酯（TPGS）是否能保护视网膜免受这种损伤。
使用40只体重500 - 600克的雄性豚鼠的右眼。将动物随机分为1组（对照组）、2组（I/R组）、3组（I/R加α-生育酚组）、4组（I/R加γ-生育酚组）和5组（I/R加TPGS组）。3组、4组和5组分别以6小时间隔进行4次皮下注射，α-生育酚、γ-生育酚和TPGS的总剂量分别为800 IU/kg、1000 IU/kg和750 IU/kg。每种物质的第一剂在视网膜缺血前5分钟给药。诱导视网膜缺血90分钟，然后再灌注24小时。在再灌注期间的6、12和18小时重复注射这三种物质。在再灌注24小时时处死动物。切取4微米厚的矢状切片，用苏木精和伊红染色进行光镜评估。在靠近视神经的矢状切片中测量每只眼睛内网状层的平均厚度（水肿），并以微米表示。
所有三种物质在缺血再灌注损伤期间对视网膜水肿的形成均显示出统计学上的显著保护作用。对照组、I/R组、I/R加α-生育酚组、I/R加γ-生育酚组和I/R加TPGS组内网状层的平均厚度分别为15.0、25.44、19.81、21.38和20.88微米。结果显示，1组（对照组）内网状层的厚度显著低于其他组（p<0.001）。I/R组的内网状层比I/R加α-生育酚组（p<0.001）、I/R加γ-生育酚组（p<0.001）和I/R加TPGS组（p<0.01）更厚。I/R加TPGS组的内网状层不比I/R加α-生育酚组和I/R加γ-生育酚组厚。与I/R加α-生育酚组相比，I/R加γ-生育酚组的内网状层显著更厚（p<0.01）。
这些实验结果表明，维生素E形式在视网膜缺血再灌注损伤期间对视网膜具有保护作用，但α-生育酚和TPGS的作用似乎比γ-生育酚大得多。
