Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits

Abstract

AIM: To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. METHODS: Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. RESULTS: During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1β (IL-1β) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1β expression. Ozurdex suppressed the expression of IL-1β, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. CONCLUSION: The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1β, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1β inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

CX3CL1/CX3CR1 Signaling Mediated Neuroglia Activation Is Implicated in the Retinal Degeneration: A Potential Therapeutic Target to Prevent Photoreceptor Death

“… 68 In the traumatic proliferative vitreoretinopathy (PVR) rabbit model, a slow-release dexamethasone implant can promote photoreceptor survival by mitigating Müller cell gliosis. 69 Recent studies also show that photobiomodulation (PBM) inhibits Müller cell activation and reduce the expression level of IL-1β and IL-6 in the light-induced RD model. 70 , 71 In this study, we show that AZD8797 inhibits the gliosis response and rescues the photoreceptors in RD mice.…”

MCC950 Ameliorates Acute Exogenous Lipoid Pneumonia Induced by Sewing Machine Oil in Ratsviathe NF-κB/NLRP3 Inflammasome Pathway

“…MCC950 down-regulated NF-ĸB, NLRP3, caspase-1 and IL-1β in the lung tissue. The transduction pathway of the NF-ĸB/NLRP3/IL-1β has been considered as essential for an early inflammatory response (17,18). In our study, RT-qPCR was performed to determine the levels of downstreamsignalling molecules.…”

Vitreous Olink proteomics reveals inflammatory biomarkers for diagnosis and prognosis of traumatic proliferative vitreoretinopathy

“…A large number of cytokines have been reported to be involved in the pathogenesis of PVR, including PDGF, VEGF, HGF, EGF, TGFa/b, FGF, IL-1, IL-6, IL-8, IL-10, TNF-a/b, IFN-g1, and GFAP (1)(2)(3)(4)(5)(6)(7). However, different immune responses and mechanisms may be active in the pathogenesis of PVR and traumatic proliferative vitreoretinopathy (TPVR) (8,9), and when it comes to TPVR-related cytokines, only IL-6, IL-8, ABCA4, TNF-a, and HGF have been mentioned in relevant reports (8,10,11).…”