RESUMEN
AIM: To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR). METHODS: A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectioning and hematoxylin and eosin (HE) staining. Activation of retinal Müller glial cells were examined by immunoblot of glial fibrillary acidic protein (GFAP). rMC-1, a retinal Müller cell line, was used for in vitro study. Expression of hypoxia-induced factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by Western-blot analysis, enzyme-linked immunosorbent assay (ELISA) or immunostaining. RESULTS: Aberrant RNV and glial activation was observed after OIR. Of note, retinal AChE was mainly expressed by retinal Müller glial cells and markedly increased in OIR mice. Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR. Moreover, ischemia-induced HIF-1α accumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention. CONCLUSION: AchE is implicated in RNV with OIR. Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.
RESUMEN
Moyamoya disease is an unusual cerebrovascular disease that is characterized by progressive occlusion of major cerebral arteries and abnormal collateralization of intracranial blood flow. The etiology of this disorder remains unknown. The diagnosis of moyamoya disease is made on the basis of angiographic findings: In its early stage there is stenosis of the supraclinoid portion of the internal carotid artery, frequently bilaterally. Later, there is enlargement of extracranial transdural collateral circulation. Surgical treatment of moyamoya disease consists of either direct anastomosis surgery (STA-MCA anastomosis) or indirect anastomosis, includingencephaloduroarteriosynangiosis (EDAS), encephalomyosynangiosis (EMS), encephalomy- oarteriosynangiosis (EMAS), encephaloduroarterio-myosy- nangiosis (EDAMS), and omentum transplantation. Direct anastomosis is the immediately effective procedure, and it is effective in case of the acute occlusive case. But its disadvantage is high incidence of the neurological deficits due to temporary stasis of blood in the cortical arteries. The double or triple anastomosis is recommended for the multiple occlusive lesion. Additionally, in a young child it may be technically difficult because of the small caliber of the STA. Therefore, indirect anastomosis is a more popular procedure than direct anastomosis except actue infarct case. We have performed the surgical treatment for 15 cases with moyamoya disease. Improvement of clinical symtoms was obtained and postoperatively good collateral circulation was confirmed on the angiogram and brain SPECT. In conclusion, among various methods of indirect anastomosis, EDAS is a safe and effective revascularization procedure for most cases of moyamoya disease.