Fu J, Lam T T, Tso M O
Georgiana Dvorak Theobald Ophthalmic Pathology Laboratory, Department of Ophthalmology and Visual Sciences, UIC Eye Center, Lions of Illinois Eye Research Institute, University of Illinois, College of Medicine 60612.
Exp Eye Res. 1992 Apr;54(4):583-94. doi: 10.1016/0014-4835(92)90137-h.
The effect of dexamethasone in two regimens on retinal photic injury was studied in Lewis albino rats that were exposed to 24 hr of continuous green fluorescent light. Under regimen 1, dexamethasone was given at a daily dosage of 1 mg kg-1 for 8 days, starting 6 days before light exposure. Under regimen 2, dexamethasone was given at the same daily dosage for 3 days, started 1 day before light exposure. Pathologic study of the light-exposed retina, morphometric evaluation of the photoreceptor cell loss, cell counts of the macrophages in the subretinal space, and measurements of rhodopsin levels were undertaken in the dexamethasone-treated and control retinas at various times. The administration of dexamethasone in both regimens did not produce pathologic changes in the retina before light exposure, but rhodopsin levels were significantly lowered in both treated groups when compared to corresponding vehicle treated control animals. Under regimen 1, at 6 hr after light exposure, both the treated and the control groups showed comparable loss of photoreceptor cells, degeneration of the photoreceptor elements and retinal pigment epithelium, but a significantly lowered level of rhodopsin in the treated group was noted. At 6 days after exposure, the outer nuclear layer thickness, and the outer and inner segments showed significant preservation in the treated group. Also in the treated group, the number of macrophages was significantly reduced and the retinal pigment epithelial (RPE) vacuolation was markedly less. However, there was no difference in rhodopsin levels. At 14 days after exposure, the outer nuclear layer thickness and rhodopsin levels of the treated rats had significantly higher values than the controls. Under regimen 2, however, at 6 days after exposure, an ameliorative effect in the RPE was observed but there were no differences of rhodopsin levels, the outer nuclear thickness and number of macrophages between the treated and control groups. Regimen 1 was associated with a significantly higher retinal level of dexamethasone when compared with regimen 2. The ameliorative effect of dexamethasone on rat retinal photic injury may be through inhibition of lipid peroxidation, in which a high retinal level of the steroid is required.
在暴露于连续24小时绿色荧光的Lewis白化大鼠中,研究了两种给药方案的地塞米松对视网膜光损伤的影响。在方案1中,从光照前6天开始,每天以1mg/kg的剂量给予地塞米松,持续8天。在方案2中,从光照前1天开始,以相同的每日剂量给予地塞米松3天。在不同时间对接受地塞米松治疗和对照的视网膜进行光照后视网膜的病理研究、光感受器细胞损失的形态计量评估、视网膜下间隙巨噬细胞的细胞计数以及视紫红质水平的测量。两种方案中地塞米松的给药在光照前均未在视网膜中产生病理变化,但与相应的赋形剂处理的对照动物相比,两个治疗组中的视紫红质水平均显著降低。在方案1中,光照后6小时,治疗组和对照组的光感受器细胞损失、光感受器元件和视网膜色素上皮的变性相当,但治疗组中视紫红质水平显著降低。暴露后6天,治疗组的外核层厚度以及外段和内段显示出显著的保留。同样在治疗组中,巨噬细胞数量显著减少,视网膜色素上皮(RPE)空泡化明显减轻。然而,视紫红质水平没有差异。暴露后14天,治疗大鼠的外核层厚度和视紫红质水平显著高于对照组。然而,在方案2中,暴露后6天,观察到RPE有改善作用,但治疗组和对照组之间视紫红质水平、外核厚度和巨噬细胞数量没有差异。与方案2相比,方案1的视网膜地塞米松水平显著更高。地塞米松对大鼠视网膜光损伤的改善作用可能是通过抑制脂质过氧化,其中需要高视网膜水平的类固醇。