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A novel human opsin in the inner retina - PubMed

  • ️Sat Jan 01 2000

A novel human opsin in the inner retina

I Provencio et al. J Neurosci. 2000.

Abstract

Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye. In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.

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Figures

Fig. 1.
Fig. 1.

Melanopsin differs from other human opsins.A, Structure of melanopsin gene. The 5′ and 3′ untranslated regions of exons 1 and 10, respectively, are indicated inwhite. B, Comparison of human melanopsin, rhodopsin (Nathans and Hogness, 1984), blue cone opsin (Nathans et al., 1986), red and green cone opsins (Nathans et al., 1986), RGR (Shen et al., 1994), peropsin (Hui et al., 1997), and encephalopsin (Blackshaw and Snyder, 1999) ORFs. Portions of the ORFs corresponding to the transmembrane domains are shown in white and are labeled. Positions of introns are indicated (▾), and the respective chromosomal locations are displayed to the right.

Fig. 2.
Fig. 2.

Human melanopsin is expressed in the eye. RT-PCR from multiple human tissues of melanopsin (334 bp) and the GAPDH positive control (600 bp). The faint melanopsin product from RPE/choroid may have resulted from retinal contamination during dissection. Melanopsin is not expressed in the other tissues examined.

Fig. 3.
Fig. 3.

Alignment of human and mouse melanopsin-deduced amino acid sequences. Sequences were aligned with ClustalW 1.6 (Thompson et al., 1994). Predicted transmembrane domains areboxed and were determined by homology toXenopus melanopsin (Provencio et al., 1998b). The Schiff's base lysine (▪) and the invertebrate-like tyrosine counterion (●) are indicated.

Fig. 4.
Fig. 4.

Melanopsin is expressed in the monkey inner retina. Bright-field (A) and dark-field (B) photomicrographs of a section of monkey retina probed with an antisense monkey melanopsin riboprobe.C, An adjacent section probed with a sense control riboprobe. GC, Ganglion cell layer; INL, inner nuclear layer; OD, optic disk; P, photoreceptor layer. Scale bar, 150 μm.

Fig. 5.
Fig. 5.

Melanopsin is expressed in the mouse inner retina.A, Cross-section of a 10-d-old mouse eye probed with an antisense mouse melanopsin riboprobe. B,C, Bright-field and dark-field photomicrographs of indicated cell within the amacrine cell layer in A.D, E, Bright-field and dark-field photomicrographs of indicated cell pair within the ganglion cell layer in A. GC, Ganglion cell layer;INL, inner nuclear layer; P, photoreceptor layer. Scale bars: A, 250 μm;B, 50 μm.

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