Cyclic nucleotide metabolism in inherited retinopathy in collies: A biochemical and histochemical study

Cyclic nucleotide metabolism in collies afflicted with early onset inherited retinal dysplasia was investigated with biochemical and histochemical methods. 3′,5′-Guanosine monophosphate (cyclic GMP) levels in the affected retinas were 10 times higher than those in the control retinas during postnatal development of the normal photoreceptor outer segments (2-8 weeks). Cyclic AMP levels were similar in both affected and control retinas. During this period, cyclic GMP phosphodiesterase (PDE) activity was 25% lower in retinal homogenates of the affected animals than in those of the normals. The PDE activity in both normal and affected retinas was found to be calmodulin-independent. Electron microscopically, some of the outer segments of the photoreceptors in affected retinas appeared normal; most showed lamellar breakdown. By ultrastructural histochemistry, little cyclic GMP PDE activity was localized in the abnormal outer segments, while normal-appearing outer segments contained abundant reaction product in both control and affected retinas. The high levels of cyclic GMP in this collie disease are similar to those found in other models of inherited retinal dystrophy and further confirm cyclic nucleotide involvement in photoreceptor degeneration.