Publication Date
11-15-2022
Journal
International Journal of Molecular Sciences
DOI
10.3390/ijms232214069
PMID
36430547
PMCID
PMC9695972
PubMedCentral® Posted Date
11-15-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Brain-Derived Neurotrophic Factor, Eye, Ligands, Nerve Growth Factor, Receptor Protein-Tyrosine Kinases, Receptors, Nerve Growth Factor, Receptor, trkA, Receptor, trkB, Receptor, trkC, Eye Injuries, neurotrophins, nerve growth factor, Trk receptors, ocular surface, neurotrophic keratitis
Abstract
Neurotrophins are a family of closely related secreted proteins that promote differentiation, development, and survival of neurons, which include nerve growth factor (NGF), brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4. All neurotrophins signal through tropomyosin receptor kinases (TrkA, TrkB, and TrkC) which are more selective to NGF, brain-derived neurotrophic factor, and neurotrophin-3, respectively. NGF is the most studied neurotrophin in the ocular surface and a human recombinant NGF has reached clinics, having been approved to treat neurotrophic keratitis. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 are less studied neurotrophins in the ocular surface, even though brain-derived neurotrophic factor is well characterized in glaucoma, retina, and neuroscience. Recently, neurotrophin analogs with panTrk activity and TrkC selectivity have shown promise as novel drugs for treating dry eye disease. In this review, we discuss the biology of the neurotrophin family, its role in corneal homeostasis, and its use in treating ocular surface diseases. There is an unmet need to investigate parenteral neurotrophins and its analogs that activate TrkB and TrkC selectively.