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P. H. Tang, P. W. Goletz, R. K. Crouch; Mid/Long-Wavelength Cone Opsin Exhibit Unique Changes in Retinospatial Distribution in Rho-/- Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1298.
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© ARVO (1962-2015); The Authors (2016-present)
The classic visual cycle has been well characterized as an interaction between the retinal pigment epithelium (RPE) and both rod and cones to regenerate pigment, with the isomerase activity catalyzed by the protein RPE65. A second isomerase protein has been implicated within Müller cells of animals with cone-dominant retinae and mediates a cone-specific visual cycle, where all-trans retinol is converted to 11-cis retinal independent from the RPE. Recent evidence suggests that a similar pathway may also exist within the rod-dominant retina of mice. The purpose of this study is to determine the effects of reducing the cone-specific visual cycle activity upon the retinospatial and cellular distribution of mid/long-wavelength (M/L) and short-wavelength (S) opsins in Rho-/- mice cones, where rod formation of all-trans retinol is eliminated.
Cyclic light reared Rho-/- and C57BL6 were evaluated at 2-week intervals from postnatal week (PW) 2 to 12. Cone function was measured using light-adapted electroretinography (ERG) analysis beginning at PW4. Retinospatial M/L- and S-opsin distribution was analyzed using dual labeling with opsin-specific antibodies. Opsin distribution within the cone was analyzed within retinal cross-sections labeled with cone-specific antibodies.
Rho-/- mice exhibited an exaggerated cone response at PW2 and 4 compared to C57BL6 mice, but decreased significantly by PW12. Both M/L- and S-cone opsins localized properly to the outer segment; however, the retinospatial distribution of M/L-opsin changed. At PW2, M/L-opsin distribution extended across the dorsal-ventral axis, with both types of opsins present within cones of the central retina. By PW4, there is a significant reduction in the co-localization of opsins within central cones due to decrease in M/L-opsin presence. Central cones exclusively express S-opsin by PW8, with M/L-opsin expression confined only to cones of the dorsal retina. Overall cone density across the retina begins to decrease significantly after PW8.
These results suggest that reducing the supply of all-trans retinol for the cone-specific visual cycle induces a change in the retinospatial M/L-opsin distribution pattern within cones. This provides preliminary data to further explore the role that the cone-specific visual cycle plays in regulating protein expression within cones.
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