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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.
- Source :
-
Cells (2073-4409) . Aug2023, Vol. 12 Issue 15, p1987. 25p. - Publication Year :
- 2023
-
Abstract
- 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 µM 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 12
- Issue :
- 15
- Database :
- Academic Search Index
- Journal :
- Cells (2073-4409)
- Publication Type :
- Academic Journal
- Accession number :
- 169910730
- Full Text :
- https://doi.org/10.3390/cells12151987