Novel mutations in the <i>OPN1LW</i> and N<i>R2R3</i> genes in a patient with blue cone monochromacy

Cai, Bincui; Li, Zhiqing; Sun, Shuo; Wang, Linni; Chen, Lu; Yang, Jin; Li, Xiaorong

doi:10.1080/13816810.2018.1561902

Cited by 6 publications

(5 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, we collected some mutations associated with color vision deficiencies (Figure 6 and Figure S8). The mutations identified within the LWS-opsin are K82 ICL1 E, N94 2.45 K, V120 ECL1 M, S143 3.42 P, W177 4.50 R, C203 ECL2 R, P231 5.50 L, R247 5.66 X, P307 7.38 L, R330 8.51 Q, and G338 8.59 E(Nathans et al, 1993; Ueyama et al, 2002; Carroll et al, 2004; Ueyama et al, 2004; Mizrahi-Meissonnier et al, 2010; Cai et al, 2019; Iarossi et al, 2021; Zhu et al, 2021) (Figures 6A and S8A). It is noteworthy that the C203 ECL2 R mutation disrupts the disulfide bond linkage between C203 ECL2 and C126 3.25 , which is also observed in MWS-opsin (Figure 6B).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have reported that missense mutations in cone opsins associated with color vision deficiencies, however, the specific mechanisms remain unclear. (Weitz et al, 1992; Nathans et al, 1993; Ueyama et al, 2002; Carroll et al, 2004; Ueyama et al, 2004; Neitz et al, 2004; Mizrahi-Meissonnier et al, 2010; Cai et al, 2019; Neitz et al, 2020; Iarossi et al, 2021; Zhu et al, 2021). Our findings also provide some molecular insights from the structural perspective to color vision deficiencies.…”

Section: Discussionmentioning

confidence: 99%

“…CC-BY-NC-ND 4.0 International license perpetuity. It is made available under a preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted February 1, 2024. ; https://doi.org/10.1101/2024.01.30.577689 doi: bioRxiv preprint 1993; Ueyama et al, 2002;Carroll et al, 2004;Ueyama et al, 2004;Neitz et al, 2004;Mizrahi-Meissonnier et al, 2010;Cai et al, 2019;Neitz et al, 2020;Iarossi et al, 2021;Zhu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Cryo-EM structures of human cone visual pigments

Peng,

Li,

Jiang

et al. 2024

Preprint

View full text Add to dashboard Cite

Trichromatic color vision in humans constitutes a pivotal evolutionary adaptation, endowing individuals with the capacity to discern and discriminate a diverse spectrum of colors. This unique visual capability confers a selective advantage crucial for successful adaptation, survival, and reproductive success in the natural environment. Color vision in humans is facilitated by the red, green, and blue cone visual pigments within cone photoreceptor cells. These pigments consist of a G-protein-coupled receptor opsin apoprotein and a chromophore covalently linked to opsins. Despite the elucidated structure of rhodopsin, the structures of cone visual pigments have yet to be determined. Here, we present the cryo-EM structures of three human cone visual pigments in complex with G proteins. Our structural analysis reveals detailed interactions between cone opsins, all-trans-retinal, and G proteins, indicating their active state. We also provide a concise summary and analysis of mutations in human cone opsins, elucidating potential relationships between residue substitutions and spectral tuning. Notably, S1162.67Y, A2335.52S, Y2776.44F were found to induce a blue shift in the absorption spectrum of the red-pigment, while the substitutions W2816.48Y and K3127.43A resulted in the absence of the absorption spectrum. The structural elucidation of human cone visual pigments significantly contributes to our understanding of how distinct types of cone cells perceive light across varying wavelengths. Furthermore, it provides a deeper insight into the functioning of the human trichromatic vision system, probing the mechanisms enabling humans to perceive a broad spectrum of colors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cryo-EM structures of human cone visual pigments

Peng,

Li,

Jiang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…AMD is a common macular disease affecting elderly people, which ranks third as a cause of blindness after cataract and glaucoma. 13 At present, there is no effective treatment methods. The biggest obstacle to developing treatments is the lack of understanding of the molecular basis of disease.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the Effects of Cigarette Smokers’ Serum on RPE Cells With AMD High-Risk Alleles

Cai

Zhang

Sun

et al. 2022

Trans. Vis. Sci. Tech.

Self Cite

View full text Add to dashboard Cite

Purpose The aim of this study was to explore whether there are interactions between genetic (ARMS2/HTRA1) and environmental factors (cigarette smoking) in the pathogenesis of age-related macular degeneration (AMD). Methods Primary human retinal pigment epithelial (hRPE) cells were obtained from four donors’ eyes with AMD high-risk ARMS2/HTRA1 alleles, and two donors’ eyes with wild-type alleles were used as controls. The pooled serum from 32 smokers and 35 nonsmokers were collected and used separately to treat hRPE cells. The isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics was used to identify associated proteins and comparing the differences between AMD high-risk and low-risk HTRA1/ARMS2 alleles after exposure to smokers’ serum. Results After stimulation with the smokers’ serum, 400 differentially expressed proteins (DEPs) were detected in the high-risk allele cells. Several DEPs are involved in neuronal protein degeneration and oxidative stress pathways. The smokers’ serum stimulation or HTRA1 overexpression can both upregulate caveolin-1, which was one of the DEPs. Besides, the smokers’ serum enhanced the phagocytosis of cultured human RPE cells. Conclusions The study confirmed the AMD high-risk alleles, HTRA1, and cigarette smoking can promote AMD development by regulating caveolin-1 expression. Translational Relevance AMD high-risk alleles and environmental risk factors can promote the occurrence and development of AMD by regulating caveolin-1 expression, upregulation of which will induce apoptotic cell death in response to cellular stress in early AMD conditions.

show abstract

“…In a previous study, we used an AAV-based gene delivery approach to investigate the in vivo expression pattern and pathobiology of five cone opsin missense mutations (N94K, W177R, P307L, R330Q, and G338E) after expression in M-opsin knockout ( Opn1mw −/− ) mice ( Zhu et al, 2021 ). In this study, we characterize the disease mechanisms of three additional cone opsin missense mutants that have been shown to cause color-vison deficiency or BCM ( Neitz et al, 2004 ; Katagiri et al, 2018 ; Cai et al, 2019 ). We expressed OPN1LW cone opsin mutants K82E, P187S, and M273K specifically in Opn1mw −/− and WT cones using a cone-specific PR2.1 promoter ( Mancuso et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of red/green-cone opsin mutants K82E, P187S, M273K result in unique pathobiological perturbations to cone structure and function

Sechrest,

Barbera,

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

Long-and middle-wavelength cone photoreceptors, which are responsible for our visual acuity and color vision, comprise ~95% of our total cone population and are concentrated in the fovea of our retina. Previously, we characterized the disease mechanisms of the L/M-cone opsin missense mutations N94K, W177R, P307L, R330Q and G338E, all of which are associated with congenital blue cone monochromacy (BCM) or color-vision deficiency. Here, we used a similar viral vector-based gene delivery approach in M-opsin knockout mice to investigate the pathogenic consequences of the BCM or color-vision deficient associated L-cone opsin (OPN1LW) mutants K82E, P187S, and M273K. We investigated their subcellular localization, the pathogenic effects on cone structure, function, and cone viability. K82E mutants were detected predominately in cone outer segments, and its expression partially restored expression and correct localization of cone PDE6α’ and cone transducin γ. As a result, K82E also demonstrated the ability to mediate cone light responses. In contrast, expression of P187S was minimally detected by either western blot or by immunohistochemistry, probably due to efficient degradation of the mutant protein. M273K cone opsin appeared to be misfolded as it was primarily localized to the cone inner segment and endoplasmic reticulum. Additionally, M273K did not restore the expression of cone PDE6α’ and cone transducin γ in dorsal cone OS, presumably by its inability to bind 11-cis retinal. Consistent with the observed expression pattern, P187S and M273K cone opsin mutants were unable to mediate light responses. Moreover, expression of K82E, P187S, and M273K mutants reduced cone viability. Due to the distinct expression patterns and phenotypic differences of these mutants observed in vivo, we suggest that the pathobiological mechanisms of these mutants are distinct.

show abstract

Novel mutations in the OPN1LW and NR2R3 genes in a patient with blue cone monochromacy

Cited by 6 publications

References 8 publications

Cryo-EM structures of human cone visual pigments

Cryo-EM structures of human cone visual pigments

A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the Effects of Cigarette Smokers’ Serum on RPE Cells With AMD High-Risk Alleles

Expression of red/green-cone opsin mutants K82E, P187S, M273K result in unique pathobiological perturbations to cone structure and function

Contact Info

Product

Resources

About