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Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models.

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Τίτλος: Analysis of Keratoconus-Related Phenotypes in Two Pcsk1 Mouse Models.
Συγγραφείς: Beatty C; Medical College of Georgia, Augusta University, Augusta, GA, USA., Cai J; Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA.; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA., Yu H; Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA., Sun J; Medical College of Georgia, Augusta University, Augusta, GA, USA.; Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA., Heo Y; Medical College of Georgia, Augusta University, Augusta, GA, USA., Baratz KH; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA., Bernhisel AA; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA., Patel SV; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA., Estes AJ; Department of Ophthalmology, Augusta University, Augusta, GA, USA.; James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA, USA., Kuo AN; Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA., Liu Y; Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA.; Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA.; James and Jean Culver Vision Discovery Institute, Augusta University, Augusta, GA, USA.; Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, USA.
Πηγή: Translational vision science & technology [Transl Vis Sci Technol] 2026 Feb 02; Vol. 15 (2), pp. 3.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Association for Research in Vision and Ophthalmology Country of Publication: United States NLM ID: 101595919 Publication Model: Print Cited Medium: Internet ISSN: 2164-2591 (Electronic) Linking ISSN: 21642591 NLM ISO Abbreviation: Transl Vis Sci Technol Subsets: MEDLINE
Imprint Name(s): Original Publication: Rockville, Md. : Association for Research in Vision and Ophthalmology
Ιατρικοί όροι (MeSH): Keratoconus*/genetics , Keratoconus*/pathology , Proprotein Convertase 1*/genetics , Proprotein Convertase 1*/metabolism , Cornea*/pathology, Animals ; Disease Models, Animal ; Phenotype ; Mice ; Mice, Knockout ; Tomography, Optical Coherence ; Female ; Mice, Inbred C57BL ; Corneal Pachymetry ; Male
Περίληψη: Purpose: Previously, a variant within the Pcsk1 gene was found to segregate with the keratoconus (KC) phenotype in whole genome sequencing of a four-generation family. We aimed to evaluate a potential relation between the Pcsk1 gene and corneal phenotype in mouse models.
Methods: Two strains of Pcsk1 mice, one with a knockout (KO) and one with an N222D point mutation, were bred. Central corneal thickness (CCT) was determined using spectral domain optical coherence tomography (SD-OCT) in PC1/3+/+ (n = 12), PC1/3+/K^ (n = 14), PC1/3K^/K^ (n = 5), PC1+/+ (n = 8), PC1+/ N222D (n = 15), and PC1 N222D / N222D (n = 7) mice at 3 and 6 months of age. Pachymetry maps were generated using the Mouse Corneal Analysis Program (MCAP) to process OCT images. Hematoxylin and eosin (H&E) staining using corneal sections from these animals were used to examine morphological changes.
Results: No significant differences in corneal CCT, pachymetry, or morphology were observed among any of the mutant mice compared with their control littermates.
Conclusions: In this setting, neither the N222D point mutation nor the Pcsk1 KO affected the corneal phenotype in two mouse models. The Pcsk1 gene could contribute to keratoconus when paired with additional genetic and environmental factors, not included in this study.
Translational Relevance: Genetic factors are known to contribute to the pathogenesis of keratoconus. Although a variant in the Pcsk1 gene has been shown to segregate with keratoconus in a family, there is yet no evidence of Pcsk1 gene mutation correlating with pathogenic corneal phenotype in mouse models.
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Grant Information: R01 EY023242 United States EY NEI NIH HHS; R01 EY032960 United States EY NEI NIH HHS; P30 EY031631 United States EY NEI NIH HHS; R21 EY033961 United States EY NEI NIH HHS; R21 EY028671 United States EY NEI NIH HHS
Substance Nomenclature: EC 3.4.21.93 (Proprotein Convertase 1)
Entry Date(s): Date Created: 20260204 Date Completed: 20260707 Latest Revision: 20260707
Update Code: 20260707
PubMed Central ID: PMC12882103
DOI: 10.1167/tvst.15.2.3
PMID: 41636415
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2164-2591
DOI:10.1167/tvst.15.2.3