Structures and functions of the normal and injured human olfactory epithelium

Abstract

The olfactory epithelium (OE) is directly exposed to environmental agents entering the nasal cavity, leaving OSNs prone to injury and degeneration. The causes of olfactory dysfunction are diverse and include head trauma, neurodegenerative diseases, and aging, but the main causes are chronic rhinosinusitis (CRS) and viral infections. In CRS and viral infections, reduced airflow due to local inflammation, inflammatory cytokine production, release of degranulated proteins from eosinophils, and cell injury lead to decreased olfactory function. It is well known that injury-induced loss of mature OSNs in the adult OE causes massive regeneration of new OSNs within a few months through the proliferation and differentiation of progenitor basal cells that are subsequently incorporated into olfactory neural circuits. Although normal olfactory function returns after injury in most cases, prolonged olfactory impairment and lack of improvement in olfactory function in some cases poses a major clinical problem. Persistent inflammation or severe injury in the OE results in morphological changes in the OE and respiratory epithelium and decreases the number of mature OSNs, resulting in irreversible loss of olfactory function. In this review, we discuss the histological structure and distribution of the human OE, and the pathogenesis of olfactory dysfunction associated with CRS and viral infection.

Keywords: chronic rhinosinusitis; olfactory dysfunction; olfactory epithelium; respiratory metaplasia; viral infection.

FIGURE 1

OE structure and the distribution of the OE in mouse and human. (A) Uniform distribution of the mouse OE. In mouse, OSNs are arranged in a laminar pattern and are evenly distributed in both the dorsal and ventral regions of the OE. OSN, olfactory sensory neuron; OE, olfactory epithelium; OB, olfactory bulb; BC, basal cell; MVC, microvillar cell; SC, sustentacular cell. (B) Heterogeneous distribution of the human OE. The human OE lacks a well-defined stratified structure and is generally more sparsely distributed. It also has a lower density of OSNs than mouse. The dorsal surface of the OE contains more mature OSNs, while the ventral surface contains fewer mature OSNs.

FIGURE 2

OE injury caused by CRS and viral infection. (A) Two types of the OE injury. Left, normal human OE: OSN axons extend to the OB and form synapses with projection neurons in the OB. Middle, CRS with polyps: OE is injured by inflammatory cytokines and eosinophilic cationic proteins from eosinophils, resulting in apoptotic cell death. Right, viral infection: viruses (except COVID-19) infect OSNs directly and cause apoptotic cell death. CRS, chronic rhinosinusitis; OSN, olfactory sensory neuron; OE, olfactory epithelium; OB, olfactory bulb; BC, basal cell; MVC, microvillar cell; SC, sustentacular cell; ECP, eosinophilic cationic protein. (B) Histological changes after OE injury. Persistent inflammation and basal cell damage in the OE can inhibit axonal elongation of newly generated OSNs and/or result in a transition from olfactory to respiratory epithelium, leading to prolonged olfactory dysfunction.