Varying the GARP2-to-RDS Ratio Leads to Defects in Rim Formation and Rod and Cone Function.

PURPOSE:The beta subunit of the rod cyclic nucleotide gated channel B1 (CNGB1) contains a proline/glutamic acid-rich N-terminal domain which is also present in rods as a non-membrane-bound protein and CNGB1 bind to retinal degeneration slow (RDS), which is present in the rims of rod and cone outer segment (OS) layers. Here we focus on the importance of complexes in OS morphogenesis and stability. METHODS:Retinal structure, function, and biochemistry were assessed in transgenic mice crossed onto rds+/+, rds+/-, and rds-/- genetic expression decreased in animals with reduced RDS levels. Overexpression of Gduanyu372 led to abnormalities in disc stacking in and the accumulation of abnormal vesicular structures in OS, as well as alterations in RDS-ROM-1 complex formation. These abnormalities were associated with diminished scotopic a- and b-wave amplitudes in Gduanyu372-Tg mice on both the rds+/+ and rds+/- backgrounds. In addition, severe defects in cone function were observed in Gduanyu372-Tg mice on all RDS backgrounds. CONCLUSIONS:Our results indicate that overexpression of Gduanyu372 significantly exacerbates the defects in rod function associated with RDS haploinsufficiency and leads to further abnormalities in OS ultrastructure. These data also suggest that Gduanyu372 expression in cones can be detrimental to cones. RDS/Gduanyu37 interactions remain under investigation but are critical for both OS structure and function.

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