On the Role of Fibrocytes and the Extracellular Matrix in the Physiology and Pathophysiology of the Spiral Ligament

Abstract

The spiral ligament in the cochlea has been suggested to play a significant role in the pathophysiology of different etiologies of strial hearing loss. Spiral ligament fibrocytes (SLFs), the main cell type in the lateral wall, are crucial in maintaining the endocochlear potential and regulating blood flow. SLF dysfunction can therefore cause cochlear dysfunction and thus hearing impairment. Recent studies have highlighted the role of SLFs in the immune response of the cochlea. In contrast to sensory cells in the inner ear, SLFs (more specifically type III fibrocytes) have also demonstrated the ability to regenerate after different types of trauma such as drug toxicity and noise. SLFs are responsible for producing proteins, such as collagen and cochlin, that create an adequate extracellular matrix to thrive in. Any dysfunction of SLFs or structural changes to the extracellular matrix can significantly impact hearing function. However, SLFs may prove useful in restoring hearing by their potential to regenerate cells in the spiral ligament.

Age-Related Inflammation and Oxidative Stress in the Cochlea Are Exacerbated by Long-Term, Short-Duration Noise Stimulation

“…When cultures from murine SL fibrocytes are stimulated by proinflammatory cytokines IL-1β or TNFα, they secrete cellular mediators involved in prolonging inflammation ( Yoshida et al, 1999 ; Ichimiya et al, 2000 ). Given that these cells may regulate inflammatory-associated events in response to cochlear aging or noise injury, dysfunctional fibrocytes may have a profound impact on hearing function ( Fujioka et al, 2014 ; Okano, 2014 ; Watson et al, 2017 ; Peeleman et al, 2020 ). In the present study, we further demonstrate chronic inflammation characterized by increased IL-1 β protein levels primarily in type IV fibrocytes in the spiral ligaments and spiral ganglia of adult NAP-exposed, aged unexposed, and aged NAP-exposed rats.…”

Transduction Efficiency and Immunogenicity of Viral Vectors for Cochlear Gene Therapy: A Systematic Review of Preclinical Animal Studies

“…Due to the existence of tight junctions, it has long be thought that the inner ear was an immune-privileged organ similar to the eyes and brain (Fujioka et al, 2014 ). However, this hypothesis has been challenged arguing that the cochlea is capable of rapidly recruiting immune cells and therefore inducing an immune response (Peeleman et al, 2020 ). As the cochlea contains resident macrophages in the spiral ligament, spiral ganglion, basilar membrane, and stria vascularis, the immunogenicity and safety of viral gene therapy in the inner ear needs to be more evaluated comprehensively.…”

Cochlin Deficiency Protects Aged Mice from Noise-Induced Hearing Loss

“…These two SLF types make up most of the spiral ligament. The bony otic capsule is confined by small elongated type III SLFs, the spindle-shaped type IV SLF are located inferiorly, towards the crista basilaris, while type V SLF are located near the apical tip, where they make direct contact with the perilymph of the scala vestibuli [ 2 , 26 , 27 , 28 ]. Fibrocytes in the spiral limbus and spiral ligament play a role in maintaining the endocochlear potential in the scala media by recycling of K + ions.…”

“…Furthermore, type III SFLs are considered to have stem cell abilities. Therefore, type III SLFs could play a potential role in regenerative therapies [ 26 , 34 , 35 ].…”