No abstract

Although influenced by CCT, iCare agrees well with applanation tonometers.

In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual functions such as pupillary light reflex (PLR) and circadian photoentrainment. This photosensitivity requires melanopsin, an invertebrate opsin-like protein expressed by the ipRGCs. The precise role of melanopsin remains uncertain. One suggestion has been that melanopsin may be a photoisomerase, serving to regenerate an unidentified pigment in ipRGCs. This possibility was echoed by a recent report that melanopsin is expressed also in the mouse retinal pigment epithelium (RPE), a key center for regeneration of rod and cone pigments. To address this question, we studied mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments. Rpe65 ؊/؊ ipRGCs were Ϸ20-to 40-fold less photosensitive than normal at both single-cell and behavioral (PLR) levels but were rescued by exogenous 9-cis-retinal (an 11-cis-retinal analog), indicating the requirement of a vitamin A-based chromophore for ipRGC photosensitivity. In contrast, 9-cis-retinal was unable to restore intrinsic photosensitivity to melanopsin-ablated ipRGCs, arguing against melanopsin functioning merely in photopigment regeneration. Interestingly, exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65 ؊/؊ ipRGCs, suggesting that melanopsin could be a bistable pigment. Finally, we detected no melanopsin in the RPE and no changes in rod and cone sensitivities due to melanopsin ablation. Together, these results strongly suggest that melanopsin is the photopigment in the ipRGCs.RPE65 ͉ chromophore M elanopsin, an opsin-like protein, was first identified in dermal melanophores of Xenopus laevis (1) and subsequently was found in a small subset of retinal ganglion cells that is intrinsically photosensitive in mammals (2, 3). These intrinsically photosensitive retinal ganglion cells (ipRGCs) project predominantly to the suprachiasmatic nucleus (SCN), the intergeniculate leaflet, and the olivary pretectal nucleus (OPN) of the brain (3). These nuclei are important for circadian photoentrainment and the pupillary light reflex (PLR), accessory visual functions reporting ambient luminance rather than image formation on the retina. In melanopsin-knockout (opn4 Ϫ/Ϫ ) mice, the ipRGCs are present in normal numbers and project to the correct targets in the brain but are no longer intrinsically photosensitive (4). Thus, melanopsin is required for light detection by these cells. The PLR of opn4 Ϫ/Ϫ mice is also incomplete (4), and their circadian photoentrainment is attenuated (5, 6). In mice lacking both melanopsin and functional rods and cones, the PLR and circadian photoentrainment are abolished (7,8). Thus, the melanopsin-associated and rod-cone photoreceptive systems appear to account for all major non-image-forming visual functions.The action spectrum of the light response of ipRGCs can be fit by the absorption spectrum of a vitamin A-based photopigment with peak absorbance ( max ) at Ϸ484 nm (2). This action spectrum closel...

Cone bipolar cells of the vertebrate retina connect photoreceptors with ganglion cells to mediate photopic vision. Despite this important role, the mechanisms that regulate cone bipolar cell differentiation are poorly understood. VSX1 is a CVC domain homeoprotein specifically expressed in cone bipolar cells. To determine the function of VSX1, we generated Vsx1 mutant mice and found that Vsx1 mutant retinal cells form but do not differentiate a mature cone bipolar cell phenotype. Electrophysiological studies demonstrated that Vsx1 mutant mice have defects in their cone visual pathway, whereas the rod visual pathway was unaffected. Thus, Vsx1 is required for cone bipolar cell differentiation and regulates photopic vision perception.