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Inhibition of Inflammation and Pyroptosis mitigate Diabetic Retinopathy via Suppressing Receptor Activated NF‐kB Ligand (RANK‐l)
Author(s) -
Homme Rubens Petit Petit
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.573.5
Subject(s) - inflammation , pyroptosis , diabetic retinopathy , medicine , retina , receptor , apoptosis , occludin , cancer research , immunology , biology , endocrinology , microbiology and biotechnology , tight junction , diabetes mellitus , neuroscience , inflammasome , biochemistry
Diabetic Retinopathy (DR) characterized by leaky blood vessels causing vision distortion. DR generally manifests as an asymptomatic condition on its onset, however; in most cases, it is usually diagnosed in its proliferative phase. Currently, there is no cure and the available therapeutic efforts are generally ineffective. Current therapeutic methods are palliative in nature and only a subset of patients benefited. Many studies have shown an association of inflammation with DR pathology. The vitreous and the retina of DR individuals exhibit the presence of inflammatory markers such as TNF‐a, iNOS, and IL‐1b. An increase in inflammation has been shown to impair the tight cellular junctions via degradations of connexins (43 & 26) and Occludin and ZO‐1. This eventually leads to BRB breakdown, thus the occurrence of leaky blood vessels that are responsible for vision loss in DR patients. Receptor‐activated of NF‐kB ligand (RANK‐l) is known to regulates survival of T‐cell, which can break down the BBB for non‐neural antigen activation. We hypothesize that inflammation induces an increase in T cells expression which remains activated via RANK‐l, gradually pyroptosis resulted in the breakdown of BRB. Akita mice were treated with 5 mg/kg body weight of JSH‐23 for two weeks, they were injected intraperitoneal every other day. The level of inflammatory mediators was measured (e.g. iNOS), T cells, RANK‐l, and pyroptosis of retinal cells. Fluorescence angiography was performed as well to analyze the leakiness of retinal vessels. Eye pressure was also measured in Akita mice. The preliminary result indicated a significantly higher pressure in the eye of Akita mice compared to control. Further analyses should indicate a decrease in inflammatory mediators, microvascular leakage, pyroptosis, and eye pressure in treated Akita mice relative to non‐treated, thus vision improvement. Support or Funding Information Mahavir Singh, DVM, Ph.DA.; Akash George, Ph.D.; Naira Metreveli; Suresh C Tyagi, Ph.D. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .