Foveal Retinal Ganglion Cells Develop Altered Calcium Dynamics Weeks After Photoreceptor Ablation.

Autor:	Xu Z; Institute of Optics, University of Rochester, Rochester, New York., Kunala K; Center for Visual Science, University of Rochester Medical Center, Rochester, New York., Murphy P; Institute of Optics, University of Rochester, Rochester, New York., Patak L; Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California.; Vision Science Graduate Program, University of California Berkeley, Berkeley, California., Puthussery T; Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley, Berkeley, California.; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, California., McGregor J; Center for Visual Science, University of Rochester Medical Center, Rochester, New York.; Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York.
Jazyk:	angličtina
Zdroj:	Ophthalmology science [Ophthalmol Sci] 2024 Mar 22; Vol. 4 (5), pp. 100520. Date of Electronic Publication: 2024 Mar 22 (Print Publication: 2024).
DOI:	10.1016/j.xops.2024.100520
Abstrakt:	Purpose: Physiological changes in retinal ganglion cells (RGCs) have been reported in rodent models of photoreceptor (PR) loss, but this has not been investigated in primates. By expressing both a calcium indicator (GCaMP6s) and an optogenetic actuator (ChrimsonR) in foveal RGCs of the macaque, we reactivated RGCs in vivo and assessed their response in the weeks and years after PR loss. Design: We used an in vivo calcium imaging approach to record optogenetically evoked activity in deafferented RGCs in primate fovea. Cellular scale recordings were made longitudinally over a 10-week period after PR ablation and compared with responses from RGCs that had lost PR input >2 years prior. Participants: Three eyes received PR ablation, the right eye of a male Macaca mulatta (M1), the left eye of a female Macaca fascicularis (M2), and the right eye of a male Macaca fascicularis (M3). Two animals were used for in vivo recording, 1 for histological assessment. Methods: Cones were ablated with an ultrafast laser delivered through an adaptive optics scanning light ophthalmoscope (AOSLO). A 0.5 second pulse of 25 Hz 660 nm light optogenetically stimulated RGCs, and the resulting GCaMP fluorescence signal was recorded using an AOSLO. Measurements were repeated over 10 weeks immediately after PR ablation, at 2.3 years and in control RGCs. Main Outcome Measures: The calcium rise time, decay constant, and sensitivity index of optogenetic-mediated RGC were derived from GCaMP fluorescence recordings from 221 RGCs (animal M1) and 218 RGCs (animal M2) in vivo . Results: After PR ablation, the mean decay constant of the calcium response in RGCs decreased 1.5-fold (standard deviation 1.6 ± 0.5 seconds to 0.6 ± 0.3 seconds) over the 10-week observation period in subject 1 and 2.1-fold (standard deviation 2.5 ± 0.5 seconds to 1.2 ± 0.2 seconds) within 8 weeks in subject 2. Calcium rise time and sensitivity index were stable. Optogenetic reactivation remained possible 2.3 years after PR ablation. Conclusions: Altered calcium dynamics developed in primate foveal RGCs in the weeks after PR ablation. The mean decay constant of optogenetic-mediated calcium responses decreased 1.5- to twofold. This is the first report of this phenomenon in primate retina and further work is required to understand the role these changes play in cell survival and activity. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. (© 2024 by the American Academy of Ophthalmology.)
Databáze:	MEDLINE
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