Early onset of age-related changes in the retina of cystine/glutamate antiporter knockout mice.

Autor: Martis RM; Dept. Physiology, School of Medical Sciences, University of Auckland, New Zealand; School of Optometry and Vision Science, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand., Knight LJ; Dept. Physiology, School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand., Acosta ML; School of Optometry and Vision Science, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand; Centre for Brain Research, University of Auckland, New Zealand., Black J; School of Optometry and Vision Science, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand., Ng R; School of Optometry and Vision Science, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand., Ji LCL; School of Optometry and Vision Science, University of Auckland, New Zealand., Donaldson PJ; Dept. Physiology, School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand., Lim JC; Dept. Physiology, School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand. Electronic address: j.lim@auckland.ac.nz.
Jazyk: angličtina
Zdroj: Experimental eye research [Exp Eye Res] 2023 Feb; Vol. 227, pp. 109364. Date of Electronic Publication: 2022 Dec 28.
DOI: 10.1016/j.exer.2022.109364
Abstrakt: To determine the role of the cystine/glutamate antiporter on retinal structure and function, retinas of C57Bl/6J wild-type and xCT knockout mice, lacking the xCT subunit of the cystine/glutamate antiporter were examined from 6 weeks to 12 months of age. Fundoscopy, optical coherence tomography (OCT), and whole mount retinal autofluorescence imaging were used to visualise age-related retinal spots. Glial fibrillary acidic protein (GFAP) immunolabelling was used to assess retinal stress. Retinal function was evaluated using full-field and focal electroretinograms. Examinations revealed retinal spots in both wild-type and xCT knockout mice with the number of spots greater at 9 months in the knockout compared to wild-type. OCT confirmed these discrete spots were located at the retinal pigment epithelium (RPE)-photoreceptor junction and did not label with drusen markers. Whole mount lambda scans of the 9 month xCT knockout retinas revealed that the photoreceptor autofluorescence matched the spots, suggesting these spots were retinal debris. GFAP labelling was increased in knockout retinas compared to wild-type indicative of retinal stress, and the discrete spots were associated with migration of microglia/macrophages to the RPE-retina intersection. OCT revealed that the superior retina was thinner at 9 months in knockout compared to wild-type mice due to changes to the outer nuclear and photoreceptor layers. While global retinal function was not affected by loss of xCT, focal changes in retinal function were detected in areas where spots were present. Tother these results suggest that the xCT KO mice exhibit features of accelerated ageing and suggests that this mouse model may be useful for studying the underlying cellular pathways in retinal ageing.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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