| Autor: |
Gavin W. Roddy, MD, PhD, Darrell Kohli, MD, Parvin Niknam, PhD, Mohammed E. Omer, MBBS, Uttio Roy Chowdhury, PhD, Kjersten J. Anderson, Johann M. Pacheco Marrero, MD, Tommy A. Rinkoski, MS, Michael P. Fautsch, PhD |
| Jazyk: |
angličtina |
| Rok vydání: |
2025 |
| Předmět: |
|
| Zdroj: |
Ophthalmology Science, Vol 5, Iss 1, Pp 100590- (2025) |
| Druh dokumentu: |
article |
| ISSN: |
2666-9145 |
| DOI: |
10.1016/j.xops.2024.100590 |
| Popis: |
Purpose: To investigate subconjunctival administration of a single-stranded, adeno-associated virus, serotype 2, engineered to express stanniocalcin-1 with a FLAG tag (ssAAV2-STC-1-FLAG) as a novel sustained (IOP) lowering agent with a reduced ocular surface side effect profile. Design: In vivo preclinical investigation in mice. Subjects: C57BL/6J, DBA/2J, prostaglandin F (FP) receptor knockout mice. Methods: Normotensive C57BL/6J mice were treated with a subconjunctival injection of ssAAV2-STC-1-FLAG (2 μL; 6 × 109 viral genomes [VGs]) in 1 eye and the same volume and concentration of ssAAV2-green fluorescent protein (GFP) or the same volume of phosphate-buffered saline in the fellow eye. Ocular hypertensive DBA/2J mice were subconjunctivally injected with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Steroid-mediated ocular hypertension was induced in C57BL/6J mice with weekly injections of dexamethasone into the conjunctival fornix, and mice were then injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or ssAAV2-GFP. Prostaglandin F receptor knockout mice were injected subconjunctivally with 6 × 109 VGs of ssAAV2-STC-1-FLAG or phosphate-buffered saline. An identical vector was constructed without the FLAG tag (ssAAV2-STC-1) and evaluated in normotensive C57BL/6J mice. Intraocular pressure was assessed using the Tonolab tonometer for all experiments. Tumor necrosis factor alpha (TNFα), a marker of ocular surface inflammation, was compared between subconjunctivally delivered ssAAV2-STC-1-FLAG and other treatments including daily topical latanoprost. Main Outcome Measures: Intraocular pressure assessment. Results: Subconjunctival delivery of ssAAV2-STC-1-FLAG significantly reduced IOP for 10 weeks post injection in normotensive mice. Maximal IOP reduction was seen at week 3 postinjection (17.4%; 17.1 ± 0.8 vs. 14.1 ± 0.8 mmHg, P |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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