Feasibility of producing sufficient L/M opponency to support red green colour vision by coexpressing an L pigment transgene in a subset of M cone photoreceptors of protanopes

Abstract

We are developing gene therapy methods in an attempt to expand colour vision in dichromats. A viral vector carrying an L opsin gene is administered by subretinal injection to protanopic squirrel monkeys. To estimate the amount of L photopigment required within a subset of the endogenous M cones to produce an opponent difference equivalent to that of human trichromats, the relationship between L/M spectral separation and colour vision behavior was examined. Chromatic sensitivity was measured using the Colour Assessment and Diagnosis test in normal trichromats and 250 colour-deficient observers. Twenty-three subjects from this group were selected for genetic analysis to determine the spectral separation between L and M pigments. Red-green chromatic sensitivity exhibited a nonlinear relationship with photopigment proximity, indicating that observers would not show a reduction in colour discrimination sensitivity that could be reliably classified as just outside the normal range until the L/M separation is reduced to about 12 nm or less. The size of the L/M opponent response was then extrapolated for the range of L/M separations and these were converted to equivalent differences between an M cone class and one coexpressing L plus M. Accordingly, in a protanope, a subclass of transduced cones with a 1:1 mixture of L and M pigment would produce an amplitude similar to a trichromat with an L/M separation of 15 nm. As few as 1L:3M photopigment molecules within a subset of M cones would produce an opponent difference equivalent to that of anomalous trichromats with 7 nm of separation and hence relatively good colour discrimination sensitivity.

Footnotes

 Supported by the National Institutes of Health grants R03EY014056, EY09303, EY09620, T32EY014537, an NEI Core Grant for Vision Research EY01981, the Harry J. Heeb Foundation, and Research to Prevent Blindness.