Fig 1.
Representative clinical images and data of XLRS patients.
(A) Fundus exhibiting spoke wheel pattern like schisis at the macula (indicated by arrow). (B) Optical coherence tomography showing splitting of the inner retinal layers. (C) Electroretinogram showing reduced waveforms of rod and cone responses, a negative b-wave pattern noted on standard combined response (circled).
Table 1.
List of XLRS patients and their clinical characteristics.
Table 2.
RS1 mutations identified in the study and their secretion profiles.
Fig 2.
Tertiary structure and RMSD graph of WT and RS1 mutants inferring differences in backbone stability.
In the tertiary structure, helices are shown in red, sheets in yellow, loops in cyan, mutation spots in magenta with the residue label and disulphide bonds in orange colour. Diff RMSD value (Å) specified in each graph represents the average difference in the RMSD value (Å) of every mutant in comparison to the wild type.
Table 3.
Structural effects of various monomeric RS1 mutations as inferred by in silico analysis.
Fig 3.
Double octameric structure of wild type retinoschisin and its mutants visualized using pymol.
The red coloured regions (represented by an arrow) indicate the mutation points in each mutant structure.
Table 4.
Hydrophobic and hydrophilic effects of multimeric RS1 mutant structures inferred by in silico analysis.
Fig 4.
Immunoblot analysis of WT and RS1 mutants in cellular and secreted fractions of COS7 cells.
RS1 was detected using anti-FLAG antibody after 72 hours of transfection. Un-transfected lane served as negative control.
Fig 5.
Immunocytochemistry displaying expression and distribution of WT RS1 and various non-secreted RS1 mutants.
RS1 immunoreactivity (anti-FLAG antibody) is shown in green while the nucleus is stained blue using DAPI.
Table 5.
Comparison of ocular features between non-secreted and secreted XLRS groups.
Table 6.
Comparison of ERG parameters between control samples and XLRS patients showing non-secreted or secreted or protein profile.
Table 7.
Clinical data of XLRS patients showing non-secreted RS1 profile.
Fig 6.
Picture illustrating the hypothetical secretory phenomenon of RS1.
(A) Hypothetical mechanism I showing plasma membrane localization of RS1 as the primary event, followed by its secretion into the extracellular side. (B) Hypothetical mechanism II showing extracellular secretion of RS1 as the primary event, followed by its localization to the plasma membrane.