Ion channels in dry eye disease

Abstract

Dry eye disease (DED) which affects millions of people worldwide is an ocular surface disease that is strongly associated with pain, discomfort, and visual disturbances. Altered tear film dynamics, hyperosmolarity, ocular surface inflammation, and neurosensory abnormalities are the key contributors to DED pathogenesis. The presence of discordance between signs and symptoms of DED in patients and refractoriness to current therapies in some patients underpin the need for studying additional contributors that can be modulated. The presence of electrolytes or ions including sodium, potassium, chloride, bicarbonate, calcium, and magnesium in the tear fluid and ocular surface cells contribute to ocular surface homeostasis. Ionic or electrolyte imbalance and osmotic imbalance have been observed in DED and feed-forward interaction between ionic imbalances and inflammation alter cellular processes in the ocular surface resulting in DED. Ionic balances in various cellular and intercellular compartments are maintained by dynamic transport via ion channel proteins present in cell membranes. Hence, alterations in the expression and/or activity of about 33 types of ion channels that belong to voltage-gated channels, ligand-gated channels, mechanosensitive ion channel, aquaporins, chloride ion channel, sodium–potassium–chloride pumps or cotransporters have been investigated in the context of ocular surface health and DED in animal and/or human subjects. An increase in the expression or activity of TRPA1, TRPV1, Nav1.8, KCNJ6, ASIC1, ASIC3, P2X, P2Y, and NMDA receptor have been implicated in DED pathogenesis, whereas an increase in the expression or activity of TRPM8, GABAA receptor, CFTR, and NKA have been associated with resolution of DED.

Measurement of dehydration rate in vitro from SMILE-derived corneal stromal lenses

“…The fluid dynamics of the cornea is a key indicator of eye health, and it is disturbed in many cornea-related degenerative vision diseases. Studies have found that fluid dynamics can affect the barrier function of the corneal endothelium, corneal transparency, and the stability of tear film [9,10] . Therefore, understanding the water content and fluid dynamics of the cornea is necessary.…”

The Molecular Mechanisms Responsible for Tear Hyperosmolarity-Induced Pathological Changes in the Eyes of Dry Eye Disease Patients

“…When sensory neurons in the cornea and conjunctiva detect changes in osmolarity, they transmit signals to the lacrimal glands, initiating tear secretion [18]. A large number of experimental and clinical studies have demonstrated that transient receptor potential (TRP) channels are mainly responsible for the neural regulation of tear production [18][19][20][21][22][23][24][25][26][27][28]. TRP channels belong to a heterogeneous superfamily of widely expressed, functionally varied cation channels that display intricate regulation patterns and are sensitive to a variety of stimuli, including THO [23,24].…”

“…A large number of experimental and clinical studies have demonstrated that transient receptor potential (TRP) channels are mainly responsible for the neural regulation of tear production [18][19][20][21][22][23][24][25][26][27][28]. TRP channels belong to a heterogeneous superfamily of widely expressed, functionally varied cation channels that display intricate regulation patterns and are sensitive to a variety of stimuli, including THO [23,24]. Among various TRP channels, the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are dominantly expressed in sensory neurons of the cornea and conjunctiva [22][23][24].…”

“…TRP channels belong to a heterogeneous superfamily of widely expressed, functionally varied cation channels that display intricate regulation patterns and are sensitive to a variety of stimuli, including THO [23,24]. Among various TRP channels, the transient receptor potential melastatin 8 (TRPM8) and transient receptor potential vanilloid 1 (TRPV1) are dominantly expressed in sensory neurons of the cornea and conjunctiva [22][23][24]. TRP channels are essential for normal neuronal functioning and play a crucial role in sensory perception, neuronal excitability, and synaptic transmission [25].…”

“…In addition to sensory transduction, TRP channels play a crucial role in the regulation of corneal integrity, wound healing, and tear film homeostasis [22][23][24][25].…”