Light Responses in Rods of Vitamin A–Deprived Xenopus

Vitamin A is the precursor to 11-cis retinal, the chromophore that binds to opsin to produce rhodopsin, the light-absorbing pigment.1 Without vitamin A, the amount of free opsin increases, leading to a loss in quantum catch and sensitivity that resembles the desensitization caused by bright, bleaching lights.2,3 Long-term vitamin A deprivation causes retinal degeneration in mammals4,5 but not in Xenopus.2,6 Mutations that produce constitutive activation of phototransduction cause retinal degeneration in mammals.7 The point mutation G90D in rhodopsin is associated with congenital stationary night blindness.8-10 Mutations in RPE65, the gene that codes for retinoid isomerase in the pigment epithelium,11,12 cause Leber congenital amaurosis.13 Constitutive activation of phototransduction by bleaching adaptation14 or caused by mutations in rhodopsin9,15,16 leads to desensitization, speeding up of the light response, faster cGMP turnover, and a reduction of the dark circulating currents. The lack of chromophore in RPE65−/− mice produces similar effects.17,18 However, the precise link between constitutive activation of the phototransduction pathway and rod degeneration remains unclear. The equivalent light hypothesis posits that a persistent activation of the transduction pathway triggers photoreceptor degeneration.19 This idea rests on the notion that a persistent decrease in intracellular calcium triggers cell death. Understanding the reasons that constitutively active Xenopus rods do not degenerate may help us understand the mechanisms of retinal degeneration. We report that vitamin A–deprived rods in Xenopus are chronically desensitized, exhibiting constitutive activation of their phototransduction cascade and response features characteristic of light and bleaching adaptation. However, vitamin A–deprived rods preserve normal circulating current density levels by developing abnormally high levels of basal guanylate cyclase (GC) activity that counter the enhanced rates of cGMP hydrolysis.