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A visually guided swim assay for mouse models of human retinal disease recapitulates the multi-luminance mobility test in humans
Journal article   Open access   Peer reviewed

A visually guided swim assay for mouse models of human retinal disease recapitulates the multi-luminance mobility test in humans

Salma Hassan, Ying Hsu, Sara K Mayer, Jacintha Thomas, Aishwarya Kothapalli, Megan Helms, Sheila A Baker, Joseph G Laird, Sajag Bhattarai and Arlene V Drack
Saudi journal of ophthalmology, Vol.37(4), pp.313-320
11/18/2023
DOI: 10.4103/sjopt.sjopt_155_23
PMCID: PMC10752274
PMID: 38155679
url
https://doi.org/10.4103/sjopt.sjopt_155_23View
Published (Version of record) Open Access

Abstract

The purpose of this study was to develop a visually guided swim assay (VGSA) for measuring vision in mouse retinal disease models comparable to the multi-luminance mobility test (MLMT) utilized in human clinical trials. Three mouse retinal disease models were studied: Bardet-Biedl syndrome type 1 ( ), = 5; Bardet-Biedl syndrome type 10 ( ), = 11; and X linked retinoschisis (retinoschisin knockout; KO), = 5. Controls were normally-sighted mice, = 10. Eyeless mice, n = 4, were used to determine the performance of animals without vision in VGSA. Eyeless mice had a VGSA time-to-platform (TTP) 7X longer than normally-sighted controls ( < 0.0001). Controls demonstrated no difference in their TTP in both lighting conditions; the same was true for . At 4-6 M, KO and had longer TTP in the dark than controls ( = 0.0156 and = 1.23 × 10 , respectively). At 9-11 M, both BBS models had longer TTP than controls in light and dark with times similar to ( < 0.0001), demonstrating progressive vision loss in BBS models, but not in controls nor in KO. At 1 M, ERG light-adapted (cone) amplitudes were nonrecordable, resulting in a floor effect. VGSA did not reach a floor until 9-11 M. ERG combined rod/cone b-wave amplitudes were nonrecordable in all three mutant groups at 9-11 M, but VGSA still showed differences in visual function. ERG values correlate non-linearly with VGSA, and VGSA measured the continual decline of vision. ERG is no longer a useful endpoint once the nonrecordable level is reached. VGSA differentiates between different levels of vision, different ages, and different disease models even after ERG is nonrecordable, similar to the MLMT in humans.
 electroretinogram functional vision retinal degeneration light-adapted Dark-adapted visually guided swim assay

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