Abstract
Purpose :
Irreversible visual loss in retinal vein occlusion (RVO) was mainly attributed to retinal ganglion cell (RGC) death and pyroptosis, an inflammatory programmed cell death, was an critical feature of retinal neuron damage. The NLRP1, as the first identified NLRs, received great attention because of its association with neurodegenerative diseases. The aim of this study is to determined the role of NLRP1 in the pathogenesis of RVO.
Methods :
A rodent model of RVO was introduced to both NLRP1+/+ and NLRP1-/- mice by laser coagulation of major vessels after intravenous administration of Rose Bengal. Retinal blood flow dynamics, cross-sectional structures and visual function were evaluated by fluorescein angiography, optical coherence tomography and visual evoked potentials. RGCs, glias, retinal vessels were labeled on retinal whole mounts with antibodies against Brn3a, iba1 and GS-Ib4. RGC death were quantified by TUNEL. Retinal expression of NLRP1, Caspase-1 and IL-1β were determined by immunofluorescence or western-blot analysis.
Results :
Expression of NLRP1, cleaved Caspase-1 and IL-1β p17 were markedly upregulated in retinas of NLRP1+/+ RVO mice . Increased fluorescein leakage, disorganization of inner retinal layers, and attenuated p100 amplitude were observed in NLRP1+/+ RVO mice. Interestingly, all these damage were excerbated in NLRP1-/- RVO mice. Of note, NLRP1 were mainly expressed by damaged RGC; however, Caspase-1 and IL-1β were colocalized with activated microglias. TUNEL revealed more pyroptotic RCG in NLRP1-/- RVO mice compared to NLRP1+/+ mice.
Conclusions :
These results provided strong evidence that NLRP1 may act as a negatively regulator of RGC pyroptosis, making it a promising target for neural protection during RVO.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.