Irrespective of the many strategies focused on dealing with spinal cord injury (SCI), there is still no way to restore motor function efficiently or an adequate regenerative therapy. One promising method that could potentially prove highly beneficial for rehabilitation in patients is to re-engage specific neuronal populations of the spinal cord following SCI. Targeted activation may maintain and strengthen existing neuronal connections and/or facilitate the reorganization and development of new connections. BioLuminescent-OptoGenetics (BL-OG) presents an avenue to non-invasively and specifically stimulate neurons; genetically targeted neurons express luminopsins (LMOs), light-emitting luciferases tethered to light-sensitive channelrhodopsins that are activated by adding the luciferase substrate coelenterazine (CTZ). This approach employs ion channels for current conduction while activating the channels through treatment with the small molecule CTZ, thus allowing non-invasive stimulation of all targeted neurons. We previously showed the efficacy of this approach for improving locomotor recovery following severe spinal cord contusion injury in rats expressing the excitatory luminopsin 3 (LMO3) under control of a pan-neuronal and motor-neuron-specific promoter with CTZ applied through a lateral ventricle cannula. The goal of the present study was to test a new generation of LMOs based on opsins with higher light sensitivity which will allow for peripheral delivery of the CTZ. In this construct, the slow-burn Gaussia luciferase variant (sbGLuc) is fused to the opsin CheRiff, creating LMO3.2. Taking advantage of the high light sensitivity of this opsin, we stimulated transduced lumbar neurons after thoracic SCI by intraperitoneal application of CTZ, allowing for a less invasive treatment. The efficacy of this non-invasive BioLuminescent-OptoGenetic approach was confirmed by improved locomotor function. This study demonstrates that peripheral delivery of the luciferin CTZ can be used to activate LMOs expressed in spinal cord neurons that employ an opsin with increased light sensitivity.

Study Design: Retrospective cohort study. Objectives: Hypothyroidism is associated with increased perioperative risks across various surgical specialties and has recently been linked to hematologic and short-term complications following spinal fusion. However, its impact on long-term mechanical complications remains unclear. This study aims to evaluate short-term (45-day) and long-term (2-year) medical and mechanical complications in hypothyroid patients undergoing primary lumbar fusion. Methods: A retrospective analysis was conducted using the TriNetX database to identify patients who underwent lumbar fusion between 2002 and 2022 with at least 2 years of follow-up. Patients with preoperative hypothyroidism (n = 3,348, identified via ICD-10-CM code E03.9) were propensity score–matched 1:1 to euthyroid controls based on demographic and clinical risk factors. Results: After matching (n = 2850 per cohort), hypothyroid patients had higher rates of sepsis at 45 days (2.1% vs 1.3%; P = 0.019; RR: 1.62, 95% CI [1.08-2.44]). At 2 years, they had increased risks of chronic device-related infection (0.7% vs 0.3%; P = 0.019; RR: 2.27, 95% CI [1.12-4.61]), wound disruption (3.6% vs 2.7%; P = 0.031; OR: 1.35, 95% CI [1.03-1.75]), and proximal junctional kyphosis (3.2% vs 2.3%; P = 0.017; RR: 1.42, 95% CI [1.06-1.90]). No significant differences were observed in readmissions, revision surgery, or pseudoarthrosis rates. Conclusions: Hypothyroidism is a risk factor for early and late postoperative complications in patients undergoing primary lumbar fusion. Appropriate preoperative optimization with thyroid hormone supplementation to achieve euthyroid status could potentially minimize the incidence of developing notable postoperative medical and mechanical complications.

Wajahath M, et al. Clin Orthop Surg. 2026 Oct;18(5):837-847. https://doi.org/10.4055/cios25488