AbstractNeuronal regeneration in the retina is a robust, effective process in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms and cell-signaling pathways that restrict the reprogramming of Müller glia into proliferating neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this response are unknown. Using the chick retina in vivo as a model system, we investigate the role of the Nuclear Factor kappa B (NF-κB) signaling, a critical regulator of inflammation. We find that components of the NF-κB pathway are expressed by Müller glia and are dynamically regulated after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses the formation of proliferating MGPCs. Additionally, activation of NF-κB promotes glial differentiation from MGPCs in damaged retinas. With microglia ablated, the effects of NF-κB-agonists/antagonists on MGPC formation are reversed, suggesting that the context and timing of signals provided by reactive microglia influence how NF-κB-signaling impacts the reprogramming of Müller glia. We propose that NF-κB-signaling is an important signaling “hub” that suppresses the reprogramming of Müller glia into proliferating MGPCs and this “hub” coordinates signals provided by reactive microglia.

Retinal regeneration is robust in some cold-blooded vertebrates, but this process is ineffective in warm-blooded vertebrates. Understanding the mechanisms that suppress the reprogramming of Müller glia into neurogenic progenitors is key to harnessing the regenerative potential of the retina. Inflammation and reactive microglia are known to influence the formation of Müller glia-derived progenitor cells (MGPCs), but the mechanisms underlying this interaction are unknown. We used the chick model in vivo to investigate Nuclear Factor kappa B (NF-κB) signaling, a critical regulator of inflammation, during the reprogramming of Müller glia into proliferating progenitors. We find that components of the NF-κB pathway are dynamically regulated by Müller glia after neuronal damage or treatment with growth factors. Inhibition of NF-κB enhances, whereas activation suppresses the formation of proliferating MGPCs. Following microglia ablation, the effects of NF-κB-agonists on MGPC-formation are reversed, suggesting that signals provided by reactive microglia influence how NF-κB impacts Müller glia reprogramming. We propose that NF-κB is an important signaling “hub” that suppresses the reprogramming of Müller glia into proliferating MGPCs and this “hub” coordinates signals provided by reactive microglia.

OBJECTIVE The aim of this study was to determine whether cage morphology influences clinical and radiographic outcomes following short-segment transforaminal lumbar interbody fusion (TLIF) procedures. METHODS The authors retrospectively reviewed one- and two-level TLIFs at a single tertiary care center between August 2012 and November 2019 with a minimum 1-year radiographic and clinical follow-up. Two cohorts were compared based on interbody cage morphology: steerable “banana” cage or straight “bullet” cage. Patient-reported outcome measures (PROMs), radiographs, and complications were analyzed. RESULTS A total of 135 patients with 177 interbody levels were identified; 45 patients had 52 straight cages and 90 patients had 125 steerable cages. Segmental lordosis increased with steerable cages, while it decreased with straight cages (+3.8 ± 4.6 vs −1.9 ± 4.3, p < 0.001). Conversely, the mean segmental lordosis of adjacent lumbar levels decreased in the former group, while it increased in the latter group (−0.52 ± 1.9 vs +0.52 ± 2.1, p = 0.004). This reciprocal relationship results in global sagittal parameters, including pelvic incidence minus lumbar lordosis and lumbar distribution index, which did not change after surgery with either cage morphology. Multivariate analysis confirmed that steerable cage morphology, anterior cage positioning, and less preoperative index-level segmental lordosis were associated with greater improvement in index-level segmental lordosis. PROMs were improved after surgery with both cage types, and the degree of improvement did not differ between cohorts (p > 0.05). Perioperative and radiographic complications were similar between cohorts (p > 0.05). Overall reoperation rates, as well as reoperation rates for adjacent-segment disease within 2 years of surgery, were not significantly different between cohorts. CONCLUSIONS Steerable cages are more likely to lie within the anterior disc space, thus increasing index-level segmental lordosis, which is accompanied by a reciprocal change in segmental alignment at the adjacent lumbar levels. The converse relationship occurs for straight cages, with a kyphotic change at the index levels and reciprocal lordosis occurring at adjacent levels.

No abstract

CONCLUSION:The results from this first-in-man trial suggest a favorable safety and efficacy profile for the continued study of DiscSeal. Future studies evaluating DiscSeal as a minimally invasive therapy for chronic discogenic LBP are warranted.