Corneal sensation

Researchers are exploring the neural basis of ocular sensations

Dermot McGrath

Posted: Friday, November 2, 2018

Carlos Belmonte MD, PhD

Major advances have been made in recent years into understanding the characteristics and neural basis of corneal and conjunctival sensations such as dryness, discomfort and pain, Carlos Belmonte MD, PhD, said in the keynote EuCornea Medal Lecture at the 9th EuCornea Congress in Vienna.

“Ophthalmologists have traditionally dedicated very limited attention to the study of the non-visual sensory capacities of the eye. This is because pain, the most relevant symptom of disease in most medical specialties, rarely accompanies the main ocular pathologies such as cataract, retinal degeneration, refractive defects and glaucoma,” said Dr Belmonte, Professor Emeritus at the Instituto de Neurociencias, Universidad Miguel Hernandez-CSIC Spain.

This initial lack of interest has reversed rapidly in recent years with the development of invasive, sophisticated surgical procedures to treat patients suffering ocular pathologies, the increasing use of contact lenses and the high incidence of dry eye among the growing population of elderly people, noted Dr Belmonte.

Using cellular, electrophysiological and behavioural techniques, Dr Belmonte’s research has shown how corneal nerves are responsible for sensations of touch, pain, and temperature and also play an important role in the regulation of spontaneous and reflex blinking, wound healing and modulation of tear production and secretion.

Corneal nerves are functionally heterogeneous, noted Dr Belmonte: about 20% respond exclusively to noxious mechanical forces (mechano-nociceptors); 70% are additionally excited by extreme temperatures, exogenous irritant chemicals and endogenous inflammatory mediators (polymodal nociceptors); the remaining 10% are cold-sensitive and increase their discharge with moderate cooling of the cornea (cold receptors). Each of these types of sensory fibres contribute distinctly to the discomfort and pain sensations evoked by the tissue damage accompanying ocular surface disorders, he said. This damage always produces local inflammation, and a certain level of lesion of the affected nerves, which vary depending on the type of eye disorder.

For instance, lesion of ocular surface nerves is consubstantial to some surgical interventions on the eye, whereas inflammation is limited. Nerve injury also occurs, albeit in lesser degree in a number of contact lens users, in elderly and in dry eye patients. On the other hand, local inflammation of the eye surface tissues is the most relevant sign in allergic, immune and infectious eye diseases, while noxious effects on nerves are less prominent. Accordingly, intensity, quality and duration of discomfort and pain sensations in these different disorders vary markedly.

“Inflammation and nerve injury have important short- and long-term consequences on the architecture, molecular organisation and excitability of sensory neurons,” Dr Belmonte said. Under pathological conditions such as allergic keratoconjunctivitis, surgical injury or dryness of the ocular surface, the activity of ocular surface neurons changes markedly, initially as the result of short-term changes in ion channel expression secondary to local release of inflammatory agents and nerve injury and later by long-lasting modifications in gene expression, explained Dr Belmonte. This leads to the development of spontaneous activity and of abnormal responsiveness to natural stimuli, which cause spontaneous pain and dysesthesias.

Carlos Belmonte: