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Differential Effects of Experimental Retinal Detachment on S- and M/L-Cones in Rats

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Abstract

Retinal detachment is a vision-threatening condition, which occurs when the neurosensory retina is separated from its blood supply. The main purpose of this study was to examine the effect of experimental retinal detachment in rats on cone photoreceptors. Retinal detachment was induced in the eyes of rats via subretinal injection of sodium hyaluronate. Experimental detachment caused a rapid, sustained loss of short (S)- and medium/long (M/L)-wavelength cone opsins. Importantly, S-opsin+ cones were affected earlier than M/L-opsin+ cones and were affected to a greater extent than M/L-opsin+ cones throughout the duration of detachment. In comparison, to cone opsins, reductions in other cone markers—peanut agglutinin PNA and cone arrestin—were substantially less marked. These data suggest that loss of cone opsins does not reflect cone degeneration and may rather indicate prolonged downregulation of specific proteins in affected cones. This conclusion is supported by the lack of TUNEL+- cone arrestin+ double-labelled cells at the time point of greatest rod photoreceptor cell death, together with the partial recovery of cone arrestin+ cell numbers over time. Analysis of retinas that had naturally re-attached reinforced the deduction that few cones die following detachment, but also highlighted that prolonged detachment leads to deconstruction of cone segments that may not be readily reversible. Survival and functional recovery of cones following surgery for retinal detachment is vital for successful recovery of vision. The data suggest that experimental detachment in rats may offer a useful approach to model the response of S-cones to retinal detachment in humans.

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Data Availability

The datasets created during the current study are available from the corresponding author on reasonable request. No publicly available data was used in the manuscript.

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Acknowledgements

The authors are grateful to Sergi Kozirev and Mark Daymon for expert technical assistance.

Funding

This study was supported by The Royal Adelaide Hospital, Vision Research Fund, and by a grant from the Ophthalmic Research Institute of Australia.

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Authors and Affiliations

  1. Ophthalmic Research Laboratories, Discipline of Ophthalmology and Visual Sciences, University of Adelaide, Level 7 Adelaide Health and Medical Sciences Building, North Terrace, Adelaide, SA, 5000, Australia

    Glyn Chidlow, Weng Onn Chan, John P. M. Wood & Robert J. Casson

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  1. Glyn Chidlow
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  2. Weng Onn Chan
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Contributions

All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: GC, JW and RC. Establishment of rat model of retinal detachment: WOC. Acquisition of data: GC and JW. Analysis and interpretation of data: GC and JW. Drafting of the manuscript: GC. Critical revision of the manuscript for important intellectual content: JW, WOC and RC. Statistical analysis: GC and RC. Obtained funding: WOC and RC. Administrative, technical and material support: RC.

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Correspondence to Glyn Chidlow.

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A statement on the animal ethics approvals obtained prior to commencement of this study has been included in the manuscript. All housing and experimental procedures conformed with the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes, 2013, and with the ARVO Statement for the use of animals in vision and ophthalmic research.

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Chidlow, G., Chan, W.O., Wood, J.P.M. et al. Differential Effects of Experimental Retinal Detachment on S- and M/L-Cones in Rats. Mol Neurobiol 59, 117–136 (2022). https://doi.org/10.1007/s12035-021-02582-9

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