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June 1999

Is the Study of Blind Patients Useful for Understanding Light Perception?

Arch Ophthalmol. 1999;117(6):848. doi:

We appreciated the editorial by Ross,1 which raises the issue of the possible use of light by blind or visually impaired patients. In particular, there is growing evidence that the retinohypothalamic tract of some blind patients may convey photic information from the retina to the suprachiasmatic nucleus, containing the biologic clock, despite a total absence of visual perception.2 We would like to draw attention to recent observations on the basic question raised by Ross1 concerning transduction of the photic signal in some blind patients with clear ocular media. Clinical studies of the effects of light on melatonin secretion2 have suggested photic synchronization (or entrainment) of circadian rhythms in a subpopulation of blind patients, with one eye or both eyes. We know that the eyes are necessary for photic regulation of circadian rhythms, since bilaterally enucleated animals have no circadian responses to light.3 Similar photic sensitivity in blind or retinally degenerate mammalian models has also been demonstrated. For example, despite blindness and severe regression of the eye and visual pathways, the mole rat shows an intact retinal innervation of the suprachiasmatic nucleus,4 a photic entrainment of circadian rhythms,5 and photic induction of the proto-oncogene c-Fos in the suprachiasmatic nucleus.5 Moreover, mutant mice with retinal degeneration6,7 (rd/rd) and transgenic rodless mice8 are visually blind but retain photical regulation of circadian locomotor rhythms. These results suggest that, although rods may not be required, remaining middle and/or short wavelength-sensitive cone photoreceptors may be involved in mediating circadian phototransduction in the eyes of these blind animals. However, it is also possible that an unidentified conelike photoreceptor with a novel opsin or a combination of several photoreceptor classes could mediate circadian photoreception. Indeed, a recent study reported the presence of a functional opsin-based photopigment system in old rd/rd mice (photopigment chromophore 11-cis-retinaldehyde).6 A more recent study,7 which used a sensitive retrograde viral tracing technique, demonstrated a specific subclass of photoreceptors and amacrinelike cells synaptically linked to ganglion cells that project to the suprachiasmatic nucleus. These and previous findings emphasize that the neural substrate controling photic circadian responses are distinct from the visual channels subserving image formation and visual perception.

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