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Tatini Rakshit, Paul Shin-Hyun Park; Rhodopsin organization in retinal membranes of heterozygous rhodopsin knockout mice assessed by atomic force microscopy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):445.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in rhodopsin are a leading cause of autosomal dominant retinitis pigmentosa (adRP). A majority of mutations in rhodopsin causing adRP result in misfolded receptor, thereby reducing the level of properly folded receptor available for incorporation into disc membranes of rod outer segments (ROS). Heterozygous rhodopsin knockout (Rho+/-) mice provide a suitable model to study the effects of reduced rhodopsin expression levels. Atomic force microcopy (AFM) was performed on retinal samples from Rho+/- mice to investigate the impact of reduced rhodopsin expression on ROS disc membrane structure.
ROS disc membranes were isolated from the eyes of wild-type (WT) and Rho+/- mice. Disc membranes were imaged by AFM. AFM revealed the organization of rhodopsin into nanodomains. The dimensions of disc membranes and rhodopsin nanodomains were determined and analyzed.
The size of ROS disc membranes in Rho+/- mice is smaller than those in WT mice. Like rhodopsin in WT mice, rhodopsin forms nanodomains in disc membranes of Rho+/- mice. The spatial density of rhodopsin in 4-week-old Rho+/- mice was less than that of rhodopsin in 6-week-old Rho+/- mice. No difference in spatial density of rhodopsin was observed in samples from 4- and 6-week-old WT mice. The spatial density of rhodopsin in disc membranes of 6-week-old Rho+/- mice were similar to that found in disc membranes of WT mice. The average surface area of nanodomains was the same for all mice studied.
Reduced rhodopsin expression reduces the size of ROS discs. Initially, a reduction in the expression of rhodopsin decreases the density of rhodopsin in disc membranes. However, as mice age the reduced level of rhodopsin expression is overcome to achieve similar rhodopsin densities as that observed in WT mice. Thus, there appears to be a mechanism in place to achieve a constant density of rhodopsin in disc membranes. The surface area of rhodopsin nanodomains is unaffected by the reduced level of rhodopsin expression.
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