Age-related effects of optineurin deficiency in the mouse eye.

Autor: Su CC; Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan., Liu C; Departments of Ophthalmology and Radiology, Neuroscience Institute, and Tech4Health Institute, New York University Grossman School of Medicine, New York, NY 10017, USA., Adi V; Departments of Ophthalmology and Radiology, Neuroscience Institute, and Tech4Health Institute, New York University Grossman School of Medicine, New York, NY 10017, USA., Chan KC; Departments of Ophthalmology and Radiology, Neuroscience Institute, and Tech4Health Institute, New York University Grossman School of Medicine, New York, NY 10017, USA; Department of Biomedical Engineering, Tandon School of Engineering, New York University, New York, NY 11201, USA., Tseng HC; Duke Eye Center, Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: henry.tseng@duke.edu.
Jazyk: angličtina
Zdroj: Vision research [Vision Res] 2024 Nov; Vol. 224, pp. 108463. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.visres.2024.108463
Abstrakt: Optineurin (OPTN) is a gene associated with familial normal tension glaucoma (NTG). While NTG involves intraocular pressure (IOP)-independent neurodegeneration of the visual pathway that progresses with age, how OPTN dysfunction leads to NTG remains unclear. Here, we generated an OPTN knockout mouse (Optn -/ - ) model to test the hypothesis that a loss-of-function mechanism induces structural and functional eye deterioration with aging. Eye anatomy, visual function, IOP, retinal histology, and retinal ganglion cell survival were compared to littermate wild-type (WT) control mice. Consistent with OPTN's role in NTG, loss of OPTN did not increase IOP or alter gross eye anatomy in young (2-3 months) or aged (12 months) mice. When retinal layers were quantitated, young Optn -/ - mice had thinner retina in the peripheral regions than young WT mice, primarily due to thinner ganglion cell-inner plexiform layers. Despite this, visual function in Optn -/ - mice was not severely impaired, even with aging. We also assessed relative abundance of retinal cell subtypes, including amacrine cells, bipolar cells, cone photoreceptors, microglia, and astrocytes. While many of these cellular subtypes were unaffected by Optn deletion, more dopaminergic amacrine cells were observed in aged Optn -/ - mice. Taken together, our findings showed that complete loss of Optn resulted in mild retinal changes and less visual function impairment, supporting the possibility that OPTN-associated glaucoma does not result from a loss-of-function disease mechanism. Further research using these Optn mice will elucidate detailed molecular pathways involved in NTG and identify clinical or environmental risk factors that can be targeted for glaucoma treatment.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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