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; Arlene V Drack

doi:10.4103/sjopt.sjopt_155_23

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

Saudi J Ophthalmol. 2023 Nov 18;37(4):313-320. doi: 10.4103/sjopt.sjopt_155_23. eCollection 2023 Oct-Dec.

Authors

Salma Hassan^{1

2}, Ying Hsu², Sara K Mayer^{2

3}, Jacintha Thomas², Aishwarya Kothapalli², Megan Helms², Sheila A Baker⁴, Joseph G Laird⁴, Sajag Bhattarai², Arlene V Drack^{1

2

3

5}

Affiliations

¹ Department of Anatomy and Cell Biology, Biomedical Science- Cell and Developmental Biology Graduate Program, Iowa City, IA, USA.
² Department of Ophthalmology and Visual Sciences, IVR, Iowa City, IA, USA.
³ Interdisciplinary Genetics Program, University of Iowa, Iowa City, IA, USA.
⁴ Department of Biochemistry, University of Iowa, Iowa City, IA, USA.
⁵ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.

Abstract

Purpose: 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.

Methods: Three mouse retinal disease models were studied: Bardet-Biedl syndrome type 1 (Bbs1^M390R/M390R), n = 5; Bardet-Biedl syndrome type 10 (Bbs10^-/-), n = 11; and X linked retinoschisis (retinoschisin knockout; Rs1-KO), n = 5. Controls were normally-sighted mice, n = 10. Eyeless Pax6^Sey-Dey mice, n = 4, were used to determine the performance of animals without vision in VGSA.

Results: Eyeless Pax6^Sey-Dey mice had a VGSA time-to-platform (TTP) 7X longer than normally-sighted controls (P < 0.0001). Controls demonstrated no difference in their TTP in both lighting conditions; the same was true for Pax6^Sey-Dey. At 4-6 M, Rs1-KO and Bbs10^-/- had longer TTP in the dark than controls (P = 0.0156 and P = 1.23 × 10^-8, respectively). At 9-11 M, both BBS models had longer TTP than controls in light and dark with times similar to Pax6^Sey-Dey (P < 0.0001), demonstrating progressive vision loss in BBS models, but not in controls nor in Rs1-KO. At 1 M, Bbs10^-/- 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.

Conclusion: 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.

Keywords: Dark-adapted; electroretinogram; functional vision; light-adapted; retinal degeneration; visually guided swim assay.