Role of NLRP3 in the immunopathogenesis of neurodegenerative eye diseases
- 作者: Balatskaya N.V.1, Gavrilova T.V.2, Kinkulkina A.R.3,4, Avagyan A.S.3,4, Svitich O.A.3
-
隶属关系:
- Helmholtz National Medical Research Center of Eye Diseases
- E. Wagner Perm State Medical University
- I. Mechnikov Research Institute of Vaccines and Sera
- I. Sechenov First Moscow State Medical University (Sechenov University)
- 期: 卷 26, 编号 4 (2023)
- 页面: 485-490
- 栏目: Forum Sochi 2023
- URL: https://bakhtiniada.ru/1028-7221/article/view/253431
- DOI: https://doi.org/10.46235/1028-7221-13985-RON
- ID: 253431
如何引用文章
全文:
详细
Neurodegenerative eye pathology is one of the leading causes of visual impairment and blindness worldwide. Primary open-angle glaucoma (POAG) belongs to the group of neurodegenerative ophthalmic diseases and is characterized by a permanent or periodic increase in intraocular pressure, followed by development of typical visual field defects, decreased visual acuity and optic nerve atrophy. Recent studies show that local inflammation, triggered by the innate immune system is the first line of defense against the pathogens and tissue destruction products, playing an important role in the POAG pathogenesis. The aim was to study the neurodegenerative ophthalmic disorder in a rabbit model, and to compare the data on distribution of alleles and genotypes of the polymorphic marker rs7525979 of NLRP3 gene in the patients with POAG. At the first stage, we studied the complex tissue samples of the retina/retinal pigment epithelium (TCS/RPE) isolated from the eyes of 14 experimental animals and 7 intact rabbits without eye damage. Neurodegenerative pathology of the eye in rabbits was carried out in the Experimental Center at the Helmholtz National Medical Research Center by a single subretinal injection of 0.01 ml of 0.9% sodium chloride solution. NLRP3 gene expression levels in TCS/RPE samples were evaluated by real-time polymerase chain reaction (PCR-RV). At the second stage, peripheral blood samples were examined in patients who were diagnosed with POAG of various stages, as well as without glaucoma. DNA was isolated from blood samples, which was subsequently analyzed for the polymorphic markers study using PCR-RT technique. According to the results of the study, we noted an increased expression of the NLRP3 gene in the TCS/RPE samples from experimental animals with simulated retinal degeneration. Moreover, an association of alleles and genotypes of the NLRP3 gene was revealed in patients with POAG. The data obtained may be indicative for involvement of NLRP3 inflammasome components in development of neurodegenerative retinal lesions in POAG.
作者简介
N. Balatskaya
Helmholtz National Medical Research Center of Eye Diseases
Email: balnat07@rambler.ru
PhD (Biology), Leading Research Associate, Head, Department of Immunology and Virology, Helmholtz National Medical Research Center of Eye Diseases
俄罗斯联邦, MoscowT. Gavrilova
E. Wagner Perm State Medical University
Email: gavrilova.tv@mail.ru
PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Department of Ophthalmology, E. Wagner Perm State Medical University
俄罗斯联邦, PermAliya Kinkulkina
I. Mechnikov Research Institute of Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)
编辑信件的主要联系方式.
Email: mech.inst@mail.ru
Postgraduate Student, Department of Microbiology, Virology and Immunology, F. Erisman Institute of Public Health, I. Sechenov First Moscow State Medical University (Sechenov University); Junior Research Associate, Laboratory of Molecular Immunology, I. Mechnikov Research Institute of Vaccines and Sera
俄罗斯联邦, Moscow; MoscowA. Avagyan
I. Mechnikov Research Institute of Vaccines and Sera; I. Sechenov First Moscow State Medical University (Sechenov University)
Email: avagyan.asmik@list.ru
Student, I. Sechenov First Moscow State Medical University (Sechenov University); Laboratory Assistant, Laboratory of Molecular Immunology, I. Mechnikov Research Institute of Vaccines and Sera
俄罗斯联邦, Moscow; MoscowO. Svitich
I. Mechnikov Research Institute of Vaccines and Sera
Email: svitichoa@yandex.ru
PhD, MD (Medicine), Corresponding Member, Russian Academy of Sciences, Professor, Department of Microbiology, Virology and Immunology, F. Erisman Institute of Public Health, I. Sechenov First Moscow State Medical University (Sechenov University); Director, I. Mechnikov Research Institute of Vaccines and Sera
俄罗斯联邦, Moscow参考
- Нероева Н.В., Нероев В.В., Илюхин П.А., Кармокова А.Г., Лосанова О.А., Рябина М.В., Майбогин А.М. Моделирование атрофии ретинального пигментного эпителия // Российский офтальмологический журнал, 2020. T. 13, № 4. С. 58-63. [Neroeva N.V., Neroev V.V., Ilyukhin P.A., Karmokova A.G., Lobanova O.A., Ryabina M.V., Maybogin A.M. Modeling of retinal pigment epithelium atrophy. Rossiyskiy oftalmologicheskiy zhurnal = Russian Ophthalmological Journal, 2020, Vol. 13, no. 4, pp. 58-63. (In Russ.)]. doi: 10.21516/2072-0076-2020-13-4-58-63.
- Chi W., Li F., Chen H., Wang Y., Zhu Y., Yang X., Zhu J., Wu F., Ouyang H., Ge J., Weinreb R.N., Zhang K., ZhuoY. Caspase-8 promotes NLRP1/NLRP3 inflammasome activation and IL-1 production in acute glaucoma. Proc. Natl Acad. Sci. USA, 2014, Vol. 111, pp. 11181-11186.
- Chi W., Chen H., Li F., Zhu Y., Yin W., Zhuo Y. HMGB1 promotes the activation of NLRP3 and caspase-8 inflammasomes via NF-kappaB pathway in acute glaucoma. J. Neuroinflamm., 2015, Vol. 12, 137. doi: 10.1186/s12974-015-0360-2.50.
- Coyle S., Khan M.N., Chemaly M., Callaghan B., Doyle C., Willoughby C.E., Atkinson S.D., Gregory-Ksander M., McGilligan V. Targeting the NLRP3 Inflammasome in Glaucoma. Biomolecules, 2021, Vol. 1, no. 8, 1239. doi: 10.3390/biom11081239.
- Chen H., Deng Y., Gan X., Li Y., Huang W., Lu L., Wei L., Su L., Luo J., Zou B., Hong Y., Cao Y., Liu Y., Chi W. NLRP12 collaborates with NLRP3 and NLRC4 to promote pyroptosis inducing ganglion cell death of acute glaucoma. Mol. Neurodegener., 2020, Vol. 15, no. 1, 26. doi: 10.1186/s13024-020-00372-w.
- Kauppinen A., Paterno J.J., Blasiak J., Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell. Mol. Life Sci., 2016, Vol. 73, pp. 1765-1786.
- Shestopalov V.I., Spurlock M., Gramlich O.W., Kuehn M.H. Immune responses in the glaucomatous retina: regulation and dynamics. Cells, 2021, Vol. 10, 1973. doi: 10.3390/cells10081973.
- Tham Y.C., Li X., Wong T.Y., Quigley H.A., Aung T., Cheng C.Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology, 2014, Vol. 121, no. 11, pp. 2081-2090.
- von Herrmann K.M., Salas L.A., Martinez E.M., Young A.L., Howard J.M., Feldman M.S., Christensen B.C., Wilkins O.M., Lee S.L., Hickey W.F., Havrda M.C. NLRP3 expression in mesencephalic neurons and characterization of a rare NLRP3 polymorphism associated with decreased risk of Parkinson’s disease. N.P.J. Parkinsons Dis., 2018, Vol. 4, 24. doi: 10.1038/s41531-018-0061-5.
- Xu J., Núñez G. The NLRP3 inflammasome: activation and regulation. Trends Biochem. Sci., 2023, Vol. 48, no. 4, pp. 331-344.
- Yerramothu P., Vijay A.K., Willcox M.P. Inflammasomes, the eye and anti-inflammasome therapy. Eye, 2018, Vol. 32, pp. 491-505.
补充文件
