Impact of reduced rhodopsin expression on the structure of rod outer segment disc membranes.

Rhodopsin is the light receptor embedded in rod outer segment (ROS) disc membranes of photoreceptor cells that initiates vision via phototransduction. The relationship between rhodopsin expression and the formation of membrane structures in the ROS is unclear but important to better understand both normal function and pathological conditions. To determine the impact of reduced rhodopsin expression on the structure of ROS discs and the supramolecular organization of rhodopsin, ROS disc membrane samples from heterozygous rhodopsin knockout mice were examined by atomic force microscopy. Similar to rhodopsin in wild-type mice, rhodopsin formed nanodomains in ROS disc membranes of heterozygous knockout mice. The reduced rhodopsin expression in heterozygous knockout mice resulted in ROS disc membranes that were smaller compared to those in wild-type mice at all ages tested. Changes in ROS disc membrane properties were observed between 4 and 6 weeks of age in heterozygous knockout mice that were not present in age-matched wild-type mice. In 4 week old mice, the number and density of rhodopsin in ROS disc membranes was lower than that in age-matched wild-type mice. In contrast, 6 and 8 week old mice had more rhodopsin molecules present in disc membranes compared to 4 week old mice, which resulted in rhodopsin densities similar to those found in age-matched wild-type mice. Thus, mechanisms appear to be present that maintain a constant density of rhodopsin within ROS disc membranes even when reducing the expression of the light receptor by about half. These adaptive mechanisms, however, only occur after 4 weeks of age.