Rohrer B, Stell W K
Lions' Sight Centre, University of Calgary, Faculty of Medicine, Alberta, Canada.
Exp Eye Res. 1994 May;58(5):553-61. doi: 10.1006/exer.1994.1049.
Occlusion of the eye (form deprivation) during post-natal development leads to ocular enlargement and myopia. The chick model of form deprivation myopia (FDM) has been used to identify candidate factors that underly the control of ocular growth. The major biochemical change associated with eye enlargement is an increase in scleral cartilage proteoglycan production (Rada et al., 1991) which is reduced in recovering eyes. Thus increasing evidence suggests that in the chicken eye, two different signals are involved, one for stop (occluder off) and one for go (occluder on). Because transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) are known to act in a push-pull manner in regulating extracellular matrix, their possible roles in FDM were tested. Chicks were occluded monocularly for 8 days, after which axial dimensions were assessed using A-scan ultrasonography, and refractive errors using streak retinoscopy. Under light halothane anesthesia, the control group received daily vehicle injections into both eyes whereas the experimental groups were treated with growth factors in the occluded eye and vehicle in the unoccluded eye. It was shown that: (1) bFGF reduced FDM in a dose-dependent manner, with a 50% effective dose (ED50) of 1.05 and 1.67 ng for subconjunctival and intravitreal delivery, respectively. Both axial eye length and refraction were similarly affected. The effects were mainly confined to a decrease in vitreous chamber depth. The anterior chamber was less deep but only after intravitreal injections, whereas lens thickness was not affected at all. At maximum effect, after subconjunctival applications the bFGF-treated occluded eyes were only 0.09 +/- 0.16 mm longer than controls, which corresponded to a refractive error of -0.67 +/- 0.82 diopters (D), whereas after intravitreal applications the difference in axial eye length was -0.07 +/- 0.19 mm, corresponding to -0.3 +/- 0.52 D. (2) This effect could be mimicked by aFGF, but with a potency approximately 160 times less than that of bFGF. The aFGF rescue effect could only be demonstrated for subconjunctival delivery; high intravitreal doses (> or = 300 ng per injection) induced retinal detachment and photoreceptor degeneration, while doses of aFGF close to the ED50 for bFGF (3 ng per injection) were completely ineffective. (3) TGF-beta 1 was not found to induce myopia in unoccluded eyes, or to increase myopia in occluded eyes. It was, however, a potent inhibitor of the bFGF rescue effect, if administered together with bFGF in the subconjunctival space.(ABSTRACT TRUNCATED AT 400 WORDS)
出生后发育期间眼睛被遮挡（形觉剥夺）会导致眼球增大和近视。形觉剥夺性近视（FDM）的雏鸡模型已被用于确定控制眼球生长的潜在候选因素。与眼球增大相关的主要生化变化是巩膜软骨蛋白聚糖产量增加（拉达等人，1991年），而在恢复的眼睛中这种增加会减少。因此，越来越多的证据表明，在鸡眼中涉及两种不同的信号，一种用于停止（遮挡物移除），一种用于启动（遮挡物存在）。由于已知转化生长因子-β（TGF-β）和碱性成纤维细胞生长因子（bFGF）在调节细胞外基质时以推拉方式起作用，因此测试了它们在FDM中的可能作用。雏鸡单眼被遮挡8天，之后使用A超超声检查评估眼轴尺寸，使用带状检影法评估屈光不正。在氟烷轻度麻醉下，对照组每天双眼注射赋形剂，而实验组在被遮挡的眼睛中用生长因子治疗，未被遮挡的眼睛注射赋形剂。结果表明：（1）bFGF以剂量依赖方式减少FDM，结膜下注射和玻璃体内注射的半数有效剂量（ED50）分别为1.05和1.67纳克。眼轴长度和屈光度受到类似影响。这些影响主要局限于玻璃体腔深度的减小。前房较浅，但仅在玻璃体内注射后出现，而晶状体厚度完全不受影响。在最大效应时，结膜下应用bFGF治疗的被遮挡眼睛仅比对照组长0.09±0.16毫米，这相当于-0.67±0.82屈光度（D）的屈光不正，而玻璃体内应用后眼轴长度差异为-0.07±0.19毫米，相当于-0.3±0.52 D。（2）aFGF可模拟这种效应，但其效力比bFGF约低160倍。aFGF的挽救作用仅在结膜下给药时得到证实；高剂量玻璃体内注射（每次注射≥300纳克）会导致视网膜脱离和光感受器退化，而接近bFGF的ED50（每次注射3纳克）的aFGF剂量则完全无效。（3）未发现TGF-β1在未被遮挡的眼睛中诱导近视，或在被遮挡的眼睛中增加近视。然而，如果在结膜下间隙与bFGF一起给药，它是bFGF挽救作用的有效抑制剂。（摘要截断于400字）
