Role of NLRP3 in the immunopathogenesis of neurodegenerative eye diseases

Abstract

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.