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, 10 (4), 150-7

Constitutive Opsin Signaling: Night Blindness or Retinal Degeneration?


Constitutive Opsin Signaling: Night Blindness or Retinal Degeneration?

Janis Lem et al. Trends Mol Med.


A subset of genetic mutations in photoreceptor-specific genes results in abnormally prolonged activation of transducin-mediated photosignaling in rod cells. In humans and animal models, these mutations cause visual dysfunctions ranging from a mild stationary night blindness to severe, early-onset retinal degeneration. There are mechanistic differences between mutations causing night blindness and those causing retinal degeneration. Here, we hypothesize that mutations causing continuous activation of the visual cascade as the result, for example, of the inability of the photoreceptor to regenerate rhodopsin, lead to retinal degeneration; those mutations that can terminate signaling, even if only partially and intermittently, slow the rate of degeneration sufficiently to give rise to stationary night blindness. Furthermore, we hypothesize that a prolonged decrease in intracellular calcium concentration resulting from persistent activation is responsible for triggering apoptotic rod-cell death.

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