FIGURE SUMMARY
Title

Gene therapy for RAB28: What can we learn from zebrafish?

Authors
Moran, A.L., Fehilly, J.D., Blacque, O., Kennedy, B.N.
Source
Full text @ Vision Res.
Fig. 1

Comparison of RAB28 across species. (a) Multiple sequence alignment of human RAB28 isoform two compared with Rab28 from different model organisms. Alignment was generated using ClustalW. Colours represent percentage identity and were annotated using Jalview. (b) Phylogenetic tree of Rab28 across different model organisms. This phylogenetic tree was constructed from the alignment by Jalview using the neighbour joining method with the Blosum62 substitution matrix.

Fig. 2

(a) Schematic of wildtype zebrafish showing regular OSP with function rab28. (b) Schematic of zebrafish rab28 KO with OSP defects which can be rescued to wildtype levels upon reintroduction of Rab28 solely to the cone photoreceptors (c) as shown in Moran et al. 2022. Created using biorender.com

Fig. 3

Working Model of the effect of rab28 KO on the zebrafish retina. From the published results, the hypothesis stands that A2PE is elevated within the rab28 KO photoreceptor OS due to the defective OSP phenotype and lower levels of Abca4b in rab28 KO. Accumulation and formation of A2PE may contribute to photoreceptor cell dysfunction. (Kim et al., 2006) Figure created using BioRender.com

Fig. 4

(a) Schematic representation of creation of humanised zebrafish lines. (b) 5 dpf larval zebrafish treated with PTU. Left, rab28-/- non transgenic larvae. Right, rab28-/- larvae transgenically expressing GFP tagged human RAB28. Arrows show the left eye of each larva. (c) Expression vectors used to create RAB28 humanised zebrafish lines. Multiple sequence alignments showing identical amino acids in all model organisms for site 23 and 217. S23F and C217W mutations mapped to RAB28 isoform2 protein domains.

Acknowledgments
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Reprinted from Vision Research, 210, Moran, A.L., Fehilly, J.D., Blacque, O., Kennedy, B.N., Gene therapy for RAB28: What can we learn from zebrafish?, 108270108270, Copyright (2023) with permission from Elsevier. Full text @ Vision Res.
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