卷:12 | |
Intraocular Adeno-Associated Virus-Mediated Transgene Endothelin-1 Delivery to the Rat Eye Induces Functional Changes Indicative of Retinal Ischemia-A Potential Chronic Glaucoma Model | |
Article | |
关键词: OPEN-ANGLE GLAUCOMA; OPTIC-NERVE HEAD; DARK-ADAPTED ELECTRORETINOGRAM; OCULAR PERFUSION-PRESSURE; NORMAL-TENSION GLAUCOMA; GANGLION-CELL LOSS; IN-VIVO; NITRIC-OXIDE; OSCILLATORY POTENTIALS; INTRAVITREAL INJECTION; | |
DOI : 10.3390/cells12151987 | |
来源: SCIE |
【 摘 要 】
Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 & mu;M or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV-ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies.
【 授权许可】