Ebneter Andreas, Chidlow Glyn, Wood John P M, Casson Robert J
Ophthalmic Research Laboratories, South Australian Institute of Ophthalmology, and Department of Ophthalmology, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia.
Arch Ophthalmol. 2011 Oct;129(10):1337-44. doi: 10.1001/archophthalmol.2011.269.
To evaluate the neuroprotective effect of short-term hyperglycemia on the retinal ganglion cell body and axon in a rat model of experimental glaucoma.
Using a well-described limbal laser technique, unilateral ocular hypertension was induced in 2 groups (26 per group) of Sprague-Dawley rats. One group remained normoglycemic; the other was rendered hyperglycemic by means of an intraperitoneal injection of streptozocin. After 2 weeks of elevated intraocular pressure, axonal and retinal damage profiles were compared using several histological techniques. Immunohistochemical changes in the retina and optic nerve were also assessed.
We found convincing evidence of delayed axonal degeneration and retinal ganglion cell death in hyperglycemic rats. Axon loss was reduced by about 50% 2 weeks after induction of ocular hypertension. Survival of retinal ganglion cell perikarya increased to a similar extent in hyperglycemic rats.
The optic nerve and retinal ganglion cells are partially protected by short-term hyperglycemia in this rat model of experimental glaucoma. Energy substrate availability may therefore play a role in glaucomatous optic neuropathy.
Our findings, to some extent, support the claims of the Ocular Hypertension Treatment Study, in which diabetes appeared to protect against the conversion to glaucoma. Targeted manipulation of neuronal energy metabolism may delay optic nerve degeneration and may represent a novel neuroprotective strategy for neurodegenerative diseases of the visual system such as glaucoma.
在实验性青光眼大鼠模型中评估短期高血糖对视网膜神经节细胞胞体和轴突的神经保护作用。
采用一种已充分描述的角膜缘激光技术，在两组（每组26只）Sprague-Dawley大鼠中诱导单侧高眼压。一组维持血糖正常；另一组通过腹腔注射链脲佐菌素使其血糖升高。在眼压升高2周后，使用多种组织学技术比较轴突和视网膜损伤情况。还评估了视网膜和视神经的免疫组化变化。
我们发现高血糖大鼠存在轴突退变延迟和视网膜神经节细胞死亡的令人信服的证据。眼压升高诱导后2周，轴突损失减少约50%。高血糖大鼠视网膜神经节细胞周核的存活率也有类似程度的增加。
在该实验性青光眼大鼠模型中，视神经和视网膜神经节细胞受到短期高血糖的部分保护。因此，能量底物的可利用性可能在青光眼性视神经病变中起作用。
我们的研究结果在一定程度上支持了高眼压治疗研究的观点，即糖尿病似乎能预防青光眼的发生。对神经元能量代谢进行靶向调控可能会延缓视神经退变，可能代表一种针对青光眼等视觉系统神经退行性疾病的新型神经保护策略。
