دورية أكاديمية
أعرض في EDS

Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression.

التفاصيل البيبلوغرافية
العنوان: Altered Elastin Turnover, Immune Response, and Age-Related Retinal Thinning in a Transgenic Mouse Model With RPE-Specific HTRA1 Overexpression.
المؤلفون: Navneet S; Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States., Ishii M; Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States., Rohrer B; Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States.; Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, United States.; Ralph H. Johnson VA Medical Center, Division of Research, Charleston, South Carolina, United States.
المصدر: Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2024 Jul 01; Vol. 65 (8), pp. 34.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Association For Research In Vision And Ophthalmology (Arvo) Country of Publication: United States NLM ID: 7703701 Publication Model: Print Cited Medium: Internet ISSN: 1552-5783 (Electronic) Linking ISSN: 01460404 NLM ISO Abbreviation: Invest Ophthalmol Vis Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo)
Original Publication: St. Louis, Mosby.
مواضيع طبية MeSH: Disease Models, Animal* , Elastin*/metabolism , Elastin*/genetics , High-Temperature Requirement A Serine Peptidase 1*/genetics , High-Temperature Requirement A Serine Peptidase 1*/metabolism , Macular Degeneration*/genetics , Macular Degeneration*/metabolism , Mice, Transgenic* , Retinal Pigment Epithelium*/metabolism , Retinal Pigment Epithelium*/pathology , Tomography, Optical Coherence*, Animals ; Humans ; Mice ; Aging ; Autoantibodies/blood ; Complement C3/genetics ; Complement C3/metabolism ; Gene Expression Regulation ; Immunoglobulin G/blood ; Immunohistochemistry ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism
مستخلص: Purpose: A single-nucleotide polymorphism in HTRA1 has been linked to age-related macular degeneration (AMD). Here we investigated the potential links between age-related retinal changes, elastin turnover, elastin autoantibody production, and complement C3 deposition in a mouse model with RPE-specific human HTRA1 overexpression.
Methods: HTRA1 transgenic mice and age-matched CD1 wild-type mice were analyzed at 6 weeks and 4, 6, and 12 to 14 months of age using in vivo retinal imaging by optical coherence tomography (OCT) and fundus photography, as well as molecular readouts, focusing on elastin and elastin-derived peptide quantification, antielastin autoantibody, and total Ig antibody measurements and immunohistochemistry to examine elastin, IgG, and C3 protein levels in retinal sections.
Results: OCT imaging indicated thinning of inner nuclear layer as an early phenotype in HTRA1 mice, followed by age and age/genotype-related thinning of the photoreceptor layer, RPE, and total retina. HTRA1 mice exhibited reduced elastin protein levels in the RPE/choroid and increased elastin breakdown products in the retina and serum. A corresponding age-dependent increase of serum antielastin IgG and IgM autoantibodies and total Ig antibody levels was observed. In the RPE/choroid, these changes were associated with an age-related increase of IgG and C3 deposition.
Conclusions: Our results confirm that RPE-specific overexpression of human HTRA1 induces certain AMD-like phenotypes in mice. This includes altered elastin turnover, immune response, and complement deposition in the RPE/choroid in addition to age-related outer retinal and photoreceptor layer thinning. The identification of elastin-derived peptides and corresponding antielastin autoantibodies, together with increased C3 deposition in the RPE/choroid, provides a rationale for an overactive complement system in AMD irrespective of the underlying genetic risk.
References: Immunol Cell Biol. 2020 Apr;98(4):305-317. (PMID: 32142167)
Invest Ophthalmol Vis Sci. 2012 Nov 09;53(12):7618-24. (PMID: 23074210)
Invest Ophthalmol Vis Sci. 2010 Jan;51(1):21-7. (PMID: 19661239)
Exp Eye Res. 2011 Oct;93(4):565-7. (PMID: 21729696)
Invest Ophthalmol Vis Sci. 2003 Feb;44(2):856-65. (PMID: 12556422)
Cells. 2023 May 03;12(9):. (PMID: 37174708)
Exp Mol Pathol. 2012 Feb;92(1):64-73. (PMID: 22001380)
Proc Natl Acad Sci U S A. 2021 Jul 27;118(30):. (PMID: 34301870)
Science. 2006 Nov 10;314(5801):992-3. (PMID: 17053109)
Exp Eye Res. 2016 Sep;150:44-61. (PMID: 26220834)
Ophthalmic Genet. 2018 Jan-Feb;39(1):46-50. (PMID: 28846052)
Invest Ophthalmol Vis Sci. 2023 Mar 1;64(3):2. (PMID: 36862121)
Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1581-1594. (PMID: 30995315)
Exp Eye Res. 2015 Apr;133:3-18. (PMID: 25819450)
Cell Death Dis. 2017 Oct 5;8(10):e3061. (PMID: 28981111)
PLoS One. 2008 Jul 02;3(7):e2593. (PMID: 18596911)
Invest Ophthalmol Vis Sci. 2014 Sep 09;55(10):6514-23. (PMID: 25205867)
Ophthalmology. 2009 Mar;116(3):488-496.e2. (PMID: 19167082)
Proc Natl Acad Sci U S A. 2020 May 5;117(18):9952-9963. (PMID: 32345717)
Am J Ophthalmol. 2013 Feb;155(2):354-360.e1. (PMID: 23127751)
Invest Ophthalmol Vis Sci. 2010 Jul;51(7):3379-86. (PMID: 20207970)
Invest Ophthalmol Vis Sci. 2024 May 1;65(5):16. (PMID: 38717425)
Immunity. 2020 Aug 18;53(2):429-441.e8. (PMID: 32814029)
Clin Exp Immunol. 1993 Nov;94(2):291-6. (PMID: 8222320)
Ophthalmology. 2022 Jun;129(6):694-707. (PMID: 35149155)
Biochem J. 2015 Dec 1;472(2):169-81. (PMID: 26385991)
Invest Ophthalmol Vis Sci. 2020 Mar 9;61(3):45. (PMID: 32207814)
Am J Pathol. 2017 Dec;187(12):2841-2857. (PMID: 28941979)
Aging Cell. 2018 Aug;17(4):e12710. (PMID: 29730901)
Prog Retin Eye Res. 2023 Nov;97:101159. (PMID: 36581531)
Invest Ophthalmol Vis Sci. 2014 May 22;55(6):3842-50. (PMID: 24854852)
Redox Biol. 2019 Jun;24:101199. (PMID: 31026769)
Invest Ophthalmol Vis Sci. 2024 Feb 1;65(2):42. (PMID: 38416457)
Exp Eye Res. 2022 Sep;222:109164. (PMID: 35798060)
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14578-83. (PMID: 21844367)
Ophthalmol Retina. 2018 Aug;2(8):808-815.e1. (PMID: 31047534)
Nature. 2011 Oct 05;478(7367):76-81. (PMID: 21979047)
Science. 2006 Nov 10;314(5801):989-92. (PMID: 17053108)
Brain Res. 1985 Aug;353(2):229-39. (PMID: 4041905)
Vessel Plus. 2021;5:. (PMID: 34017939)
Nat Commun. 2019 Oct 25;10(1):4902. (PMID: 31653841)
Invest Ophthalmol Vis Sci. 2013 Mar 05;54(3):1603-12. (PMID: 23361506)
معلومات مُعتمدة: I01 BX003050 United States BX BLRD VA; I01 RX000444 United States RX RRD VA; IK6 BX004858 United States BX BLRD VA; R01 EY030072 United States EY NEI NIH HHS
المشرفين على المادة: 0 (Autoantibodies)
0 (Complement C3)
9007-58-3 (Elastin)
EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1)
EC 3.4.21.- (HTRA1 protein, human)
0 (Immunoglobulin G)
EC 3.4.21.- (Serine Endopeptidases)
0 (Eln protein, mouse)
تواريخ الأحداث: Date Created: 20240719 Date Completed: 20240719 Latest Revision: 20240724
رمز التحديث: 20240725
مُعرف محوري في PubMed: PMC11262478
DOI: 10.1167/iovs.65.8.34
PMID: 39028977
قاعدة البيانات: MEDLINE
الوصف
تدمد:1552-5783
DOI:10.1167/iovs.65.8.34