An abnormality in retinal guanosine 3,5-monophosphate (cyclic GMP) metabolism is demonstrated in the inherited rod-cone dysplasis of Irish Setter dogs. Affected visual cells are deficient in cyclic GMP phosphodiesterase activity and have elevated levels of cyclic GMP. The biochemical abnormalities observed in affected retinas of Irish Setters are similar to those in the retinas of mice with inherited retinal degeneration before visual cell degeneration begins. A defect in cyclic GMP metabolism may be characteristic of early-onset degenerative diseases of the retina, possibly including those that affect humans.

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In the teleost retina, the photoreceptors and retinal pigment epithelium (RPE) undergo extensive movements (called retinomotor movements) in response to changes in light conditions and to an endogenous circadian rhythm . Photoreceptor movements serve to reposition the light-receptive outer segments and are effected by changes in inner segment length . Melanin granule movements within the RPE cells provide a movable melanin screen for rod outer segments . In the dark (night), cones elongate, rods contract, and pigment granules aggregate to the base of the RPE cell; in the light (day), these movements are reversed . We report here that treatments that elevate cytoplasmic cyclic adenosine 3',5'-monophosphate (CAMP) provoke retinomotor movements characteristic of nighttime dark adapation, even in bright light at midday . To illustrate this response, we present a quantitative description of the effects of cyclic nucleotides on cone length in the green sunfish, Lepomis cyanellus. Cone elongation is induced when light-adapted retinas are exposed to exogenous CAMP analogues accompanied by phosphodiesterase (PDE) inhibitors (either by intraocular injection or in retinal organ culture) . Cone movement is not affected by cyclic GMP analogues . Dose-response studies indicate that the extent, but not the rate, of cone elongation is proportional to the concentration of exogenous CAMP and analogue presented . As has been reported for other species, we find that levels of CAMP are significantly higher in dark-than in light-adapted green sunfish retinas . On the basis of these observations, we suggest that CAMP plays a role in the light and circadian regulation of teleost cone length .

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