Night vision requires signaling from rod photoreceptors to adjacent bipolar cells in the retina. Mutations in the genes NYX and GRM6, expressed in ON bipolar cells, lead to a disruption of the ON bipolar cell response. This dysfunction is present in patients with complete X-linked and autosomal-recessive congenital stationary night blindness (CSNB) and can be assessed by standard full-field electroretinography (ERG), showing severely reduced rod b-wave amplitude and slightly altered cone responses. Although many cases of complete CSNB (cCSNB) are caused by mutations in NYX and GRM6, in approximately 60% of the patients the gene defect remains unknown. Animal models of human diseases are a good source for candidate genes, and we noted that a cCSNB phenotype present in homozygous Appaloosa horses is associated with downregulation of TRPM1. TRPM1, belonging to the family of transient receptor potential channels, is expressed in ON bipolar cells and therefore qualifies as an excellent candidate. Indeed, mutation analysis of 38 patients with CSNB identified ten unrelated cCSNB patients with 14 different mutations in this gene. The mutation spectrum comprises missense, splice-site, deletion, and nonsense mutations. We propose that the cCSNB phenotype in these patients is due to the absence of functional TRPM1 in retinal ON bipolar cells.

Retinitis pigmentosa (RP) is a degenerative disease of the retina leading to progressive loss of vision and, in many instances, to legal blindness at the end stage. The RP28 locus was assigned in 1999 to the short arm of chromosome 2 by homozygosity mapping in a large Indian family segregating autosomal-recessive RP (arRP). Following a combined approach of chromatin immunoprecipitation and parallel sequencing of genomic DNA, we identified a gene, FAM161A, which was shown to carry a homozygous nonsense mutation (p.Arg229X) in patients from the original RP28 pedigree. Another homozygous FAM161A stop mutation (p.Arg437X) was detected in three subjects from a cohort of 118 apparently unrelated German RP patients. Age at disease onset in these patients was in the second to third decade, with severe visual handicap in the fifth decade and legal blindness in the sixth to seventh decades. FAM161A is a phylogenetically conserved gene, expressed in the retina at relatively high levels and encoding a putative 76 kDa protein of unknown function. In the mouse retina, Fam161a mRNA is developmentally regulated and controlled by the transcription factor Crx, as demonstrated by chromatin immunoprecipitation and organotypic reporter assays on explanted retinas. Fam161a protein localizes to photoreceptor cells during development, and in adult animals it is present in the inner segment as well as the outer plexiform layer of the retina, the synaptic interface between photoreceptors and their efferent neurons. Taken together, our data indicate that null mutations in FAM161A are responsible for the RP28-associated arRP.

FAF imaging can be reliably used to detect early retinal pigment epithelial alterations in CQ/HCQ retinopathy. Ophthalmoscopy and fluorescein angiography appear to be less sensitive. With the mfERG, more retinal abnormalities were detected compared with FAF imaging.

The hypothesis that dichromatic behavior on a clinical anomaloscope can be explained by the complement and arrangement of the long- (L) and middle-wavelength (M) pigment genes was tested. It was predicted that dichromacy is associated with an X-chromosome pigment gene array capable of producing only a single functional pigment type. The simplest case of this is when deletion has left only a single X-chromosome pigment gene. The production of a single L or M pigment type can also result from rearrangements in which multiple genes remain. Often, only the two genes at the 5′ end of the array are expressed; thus, dichromacy is also predicted to occur if one of these is defective or encodes a defective pigment, or if both of them encode pigments with identical spectral sensitivities. Subjects were 128 males who accepted the full range of admixtures of the two primary lights as matching the comparison light on a Neitz or Nagel anomaloscope. Strikingly, examination of the L and M pigment genes revealed a potential cause for a color-vision defect in all 128 dichromats. This indicates that the major component of color-vision deficiency could be attributed to alterations of the pigment genes or their regulatory regions in all cases, and the variety of gene arrangements associated with dichromacy is cataloged here. However, a fraction of the dichromats (17 out of 128; 13%) had genes predicted to encode pigments that would result in two populations of cones with different spectral sensitivities. Nine of the 17 were predicted to have two pigments with slightly different spectral peaks (usually ≤ 2.5 nm) and eight had genes which specified pigments identical in peak absorption, but different in amino acid positions previously associated with optical density differences. In other subjects, reported previously, the same small spectral differences were associated with anomalous trichromacy rather than dichromacy. It appears that when the spectral difference specified by the genes is very small, the amount of residual red–green color vision measured varies; some individuals test as dichromats, others test as anomalous trichromats. The discrepancy is probably partly attributable to testing method differences and partly to a difference in performance not perception, but it seems there must also be cases in which other factors, for example, cone ratio, contribute to a person's ability to extract a color signal from a small spectral difference.

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