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Lines of investigation
The main interest of the Ocular Neurobiology Group (ONG) is to study the functional activity of sensory nerves from the ocular surface, responsible for the genesis of sensations evoked by stimulation of ocular tissues as well as for the trophic maintenance and correct moisturizing of the ocular surface. Using both, electrophysiological techniques (recording nerve activity of sensory receptors in nerve endings and axons) and psychophysical studies (analysing the evoked sensations), the ONG investigates the functional characteristics of the primary sensory neurons innervating the anterior surface of the eye with particular attention to those neurons participating in ocular sensations of dryness, discomfort and pain.
The ONG has described the sensitivity of the ocular surface to selective stimulation in healthy subjects, as well as the correlation between electrical activity in ocular sensory nerves and sensations evoked in humans; the changes in ocular sensitivity in different pathologies, after ocular refractive surgery or with the use of different ophthalmic drugs; and the role of the ocular surface innervation in blinking and in basal and reflex tearing.
At the present time, the ONG studies the neural mechanisms responsible for the regulation by CNS of ocular surface wetness, studying the molecular and cellular mechanisms underlying sensory transduction, and the role of sensory input in the reflex regulation of tear production and blinking, as well as their changes with aging.
Representative Publications
- Ocular surface information seen from the somatosensory thalamus and cortex. Velasco E, Zaforas M, Acosta MC, Gallar J and Aguilar J. The Journal of Physiology. 2024 602(7): 1405-1426 https://doi.org/10.1113/jp285008
- Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects. Merino ML, Belmonte J, Rosas J, Acosta MC., Gallar J., Belmonte C. The Ocular Surface. 2023 27: 80-88 https://doi.org/10.1016/j.jtos.2022.11.005
- A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair Velasco-Aviles S, Patel N, Casillas-Bajo A, Frutos-Rincón L, Velasco E, Gallar J, Arthur-Farraj P, Gomez-Sanchez JA, Cabedo H eLife 2022 11:e72917 https://doi.org/10.7554/eLife.72917
- Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease Kovacs I, Luna C, Quirce S, Mizerska K, Callejo G, Riestra A, Fernandez-Sanchez L, Meseguer VM, Cuenca N, Merayo-Lloves J, Acosta MC, Gasull X, Belmonte C, Gallar J Pain 2016 157(2):399 https://doi.org/10.1097/j.pain.0000000000000455
- Acid-sensing ion channels detect moderate acidifications to induce ocular pain Callejo G, Castellanos A, Castany M, Gual A, Luna C, Acosta MC, Gallar J, Giblin JP, Gasull X Pain 2015 156(3):483 https://doi.org/10.1097/01.j.pain.0000460335.49525.1-7
- Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis Acosta MC, Luna C, Quirce S, Belmonte C, Gallar J Pain 2013 154(11):2353 https://doi.org/10.1016/j.pain.2013.07.012
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Administration personnel
- Ocular surface information seen from the somatosensory thalamus and cortex. Velasco E, Zaforas M, Acosta MC, Gallar J and Aguilar J. The Journal of Physiology. 2024 602(7): 1405-1426 https://doi.org/10.1113/jp285008
- Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects. Merino ML, Belmonte J, Rosas J, Acosta MC., Gallar J., Belmonte C. The Ocular Surface. 2023 27: 80-88 https://doi.org/10.1016/j.jtos.2022.11.005
- The Contribution of TRPA1 to Corneal Thermosensitivity and Blink Regulation in Young and Aged Mice. Laura Frutos-Rincón , Carolina Luna , Fernando Aleixandre-Carrera , Enrique Velasco , Ariadna Diaz-Tahoces , Víctor Meseguer , Juana Gallar and M. Carmen Acosta. Int. J. Mol. Sci. 2023 24(16), 12620 https://doi.org/10.3390/ijms241612620
- Cyclosporine A Decreases Dryness-Induced Hyperexcitability of Corneal Cold-Sensitive Nerve Terminals. Andrea Gyenes , Zsófia Tapasztó , Susana Quirce , Carolina Luna , Laura Frutos-Rincón , Juana Gallar , M. Carmen Acosta and Illés Kovács Int. J. Mol. Sci. 2023 24(16), 13025 https://doi.org/10.3390/ijms241613025
- Effects of physical activity/exercise on tear film characteristics and dry eye associated symptoms: A literature review. Sergio Navarro-Lopez, Manuel Moya-Ramón , Juana Gallar, Gonzalo Carracedo , Adolfo Aracil-Marco Contact Lens and Anterior Eye. 2023 46(4): 101854 https://doi.org/10.1016/j.clae.2023.101854
- Functional Changes of the Ocular Surface Sensory Nerves Due to Contact Lens Use in Young Symptomatic and Asymptomatic Users. José Ángel Pastor-Zaplana; Juana Gallar; M. Carmen Acosta Investigative Ophthalmology & Visual Science. 2023 Vol. 64, 12 https://doi.org/10.1167/iovs.64.14.12
- Action potential firing and sensory transduction are sustained by membrane potential instabilities in peripheral sensory neurons. Enrique Velasco Serna, Julio Alvarez, Víctor M. Meseguer Vigueras, Juana Gallar, Karel Talavera Biophysical J. 2023 122 (3), supplement 1, 417A (Abstract) https://doi.org/10.1016/j.bpj.2022.11.2262
- A Combination of Aerobic Exercise at Fatmax and Low Resistance Training Increases Fat Oxidation and Maintains Muscle Mass, in Women Waiting for Bariatric Surgery. Picó-Sirvent I, Manresa-Rocamora A, Aracil-Marco A, Moya-Ramón M Obes Surg. 2022 32(4): 1130-1140 https://doi.org/10.1007/s11695-022-05897-1
- A genetic compensatory mechanism regulated by Jun and Mef2d modulates the expression of distinct class IIa Hdacs to ensure peripheral nerve myelination and repair Velasco-Aviles S, Patel N, Casillas-Bajo A, Frutos-Rincón L, Velasco E, Gallar J, Arthur-Farraj P, Gomez-Sanchez JA, Cabedo H eLife 2022 11:e72917 https://doi.org/10.7554/eLife.72917
- An Experimental Model of Neuro-Immune Interactions in the Eye: Corneal Sensory Nerves and Resident Dendritic Cells. Frutos-Rincón L, Gómez-Sánchez JA, Íñigo-Portugués A, Acosta MC, Gallar J. Int J Mol Sci. 2022 23(6): art 2997 - Review https://doi.org/10.3390/ijms23062997
- Editorial: Sensory Abnormalities and Primary Sensory Neurons. Masuoka T, Acosta MC, Adams DJ Front Cell Neurosci. 2022 16: art 852614 Editorial https://doi.org/10.3389/fncel.2022.852614
- Epithelial and sensory mechanisms of nasal hyperreactivity. Velasco E, Delicado-Miralles M, Hellings PW, Gallar J, Van Gerven L, Talavera K. Allergy: Eur J Allergy and Clin Immunology. 2022 77(5): 1450-1463 - Review https://doi.org/10.1111/all.15259
- Membrane potential instabilities in sensory neurons: mechanisms and pathophysiological relevance. Velasco E, Alvarez JL, Meseguer VM, Gallar J, Talavera K. Pain. 2022 163(1): 64-74 - Review https://doi.org/10.1097/j.pain.0000000000002289
- Sensorimotor effects of plasticity-inducing percutaneous peripheral nerve stimulation protocols: a blinded, randomized clinical trial Beltrá P, Ruiz-Del-Portal I, Ortega FJ, Valdesuso R, Delicado-Miralles M, Velasco E Eur J Pain 2022 26(5): 1039-1055 https://doi.org/10.1002/ejp.1928
- Small fiber neuropathy in the cornea of Covid-19 patients associated with the generation of ocular surface disease. Barros A, Queiruga-Piñeiro J, Lozano-Sanroma J, Alcalde I, Gallar J, Fernández-Vega Cueto L, Alfonso JF, Quirós LM, Merayo-Lloves J Ocul Surf. 2022 23: 40-48 https://doi.org/10.1016/j.jtos.2021.10.010
- OSDI Questions on Daily Life Activities Allow to Detect Subclinical Dry Eye in Young Contact Lens Users. Pastor-Zaplana JA, Borras F, Gallar J, Acosta MC. J Clin Med. 2022 11(9): 2626 https://doi.org/10.3390/jcm11092626
- Editorial: Eye Pain: Etiology and Therapeutic Approaches Rusciano D., Bagnoli P., Gallar J., Galor A. Front Pharmacol. 2022 13: 914809 https://doi.org/10.3389/fphar.2022.914809
- Endogenous Pain Modulation in Response to a Single Session of Percutaneous Electrolysis in Healthy Population: A Double-Blinded Randomized Clinical Trial. Varela-Rodríguez, S., Sánchez-Sánchez, J.L., Velasco, E., Delicado-Miralles, M., Sánchez-González, J.L. J Clin Med. 2022 11 (10): art. 2889 https://doi.org/10.3390/jcm11102889
- Deciphering the Action of Perfluorohexyloctane Eye Drops to Reduce Ocular Discomfort and Pain Delicado-Miralles M, Velasco E, Díaz-Tahoces A, Gallar J, Acosta MC, Aracil-Marco A Front Med (Lausanne) 2021 8:709712 https://doi.org/10.3389/fmed.2021.709712
- Optical Assessment of Nociceptive TRP Channel Function at the Peripheral Nerve Terminal. Aleixandre-Carrera F, Engelmayer N, Ares-Suarez D, Acosta MC, Belmonte C, Gallar J, Meseguer V, Binshtok AM Int J Mol Sci 2021 22(2):481 https://doi.org/10.3390/ijms22020481
- Sodium Channel Blockers Modulate Abnormal Activity of Regenerating Nociceptive Corneal Nerves After Surgical Lesion Luna C, Mizerska K, Quirce S, Belmonte C, Gallar J, Acosta MC, Meseguer V Invest Ophthalmol Vis Sci 2021 62(1):2 https://doi.org/10.1167/iovs.62.1.2
- Unilateral Corneal Insult Also Alters Sensory Nerve Activity in the Contralateral Eye Luna C, Quirce S, Aracil-Marco A, Belmonte C, Gallar J, Acosta MC Front Med 2021 8:767967 https://doi.org/10.3389/fmed.2021.767967
- Topical treatment with a mu opioid receptor agonist alleviates corneal allodynia and corneal nerve sensitization in mice Joubert F, Guerrero-Moreno A, Fakih D, Reboussin E, Gaveriaux-Ruff C, Acosta MC, Gallar J, Sahel JA, Bodineau L, Baudouin C, Rostène W, Mélik-Parsadaniantz S, Réaux-Le Goazigo A Biomed Pharmacother 2020 132:110794 https://doi.org/10.1016/j.biopha.2020.110794
- Effects of corneal injury on ciliary nerve fibre activity and corneal nociception in mice: A behavioural and electrophysiological study Joubert F, Acosta MDC, Gallar J, Fakih D, Sahel JA, Baudouin C, Bodineau L, Mélik Parsadaniantz S, Réaux-Le Goazigo A European Journal of Pain (UK) 2019 23(3):589 https://doi.org/10.1002/ejp.1332
- Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals InVivo. Goldstein RH, Barkai O, Iñigo-Portugues A, Katz B, Lev S, Binshtok AM Neuron 2019 102(4):801 https://doi.org/10.1016/j.neuron.2019.03.005
- Role of TRPM8 channels in altered cold sensitivity of corneal primary sensory neurons induced by axonal damage Piña R, Ugarte G, Campos M, Íñigo-Portugués A, Olivares E, Orio P, Belmonte C, Bacigalupo J, Madrid R Journal of Neuroscience 2019 39(41):8177 https://doi.org/10.1523/JNEUROSCI.0654-19.2019
- TRP Channels as Sensors of Chemically-Induced Changes in Cell Membrane Mechanical Properties. Startek JB, Boonen B, Talavera K, Meseguer V Int J Mol Sci 2019 20(2):371 https://doi.org/10.3390/ijms20020371
- Functional and Morphologic Alterations in Mechanical, Polymodal, and Cold Sensory Nerve Fibers of the Cornea Following Photorefractive Keratectomy Bech F, González-González O, Artime E, Serrano J, Alcalde I, Gallar J, Merayo-Lloves J, Belmonte C Invest Ophthalmol Vis Sci 2018 59(6):2281 https://doi.org/10.1167/iovs.18-24007
- Inhibitory Effect of Amitriptyline on the Impulse Activity of Cold Thermoreceptor Terminals of Intact and Tear-Deficient Guinea Pig Corneas Masuoka T, Gallar J, Belmonte C J Ocul Pharmacol Ther 2018 34(1-2):195 https://doi.org/10.1089/jop.2017.0066
- Melanopsin expression in the cornea Delwig A, Chaney SY, Bertke AS, Verweij J, Quirce S, Larsen DD, Yang C, Buhr E, Van GR, Gallar J, Margolis T, Copenhagen DR Visual Neurosci 2018 35:e004 https://doi.org/10.1017/S0952523817000359
- Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice Alcalde I, Íñigo-Portugués A, González-González O, Almaraz L, Artime E, Morenilla-Palao C, Gallar J, Viana F, Merayo-Lloves J, Belmonte C J Comp Neurol 2018 526(11):1859 https://doi.org/10.1002/cne.24454
- TRP Channels as Sensors of Bacterial Endotoxins Boonen B, Alpizar YA, Meseguer VM, Talavera K Toxins (Basel) 2018 10(8):326 https://doi.org/10.3390/toxins10080326
- Functional Properties of Sensory Nerve Terminals of the Mouse Cornea Gonzalez-Gonzalez O, Bech F, Gallar J, Merayo-Lloves J, Belmonte C Invest Ophthalmol Vis Sci 2017 58(1):404 https://doi.org/10.1167/iovs.16-20033
- Abnormal activity of corneal cold thermoreceptors underlies the unpleasant sensations in dry eye disease Kovacs I, Luna C, Quirce S, Mizerska K, Callejo G, Riestra A, Fernandez-Sanchez L, Meseguer VM, Cuenca N, Merayo-Lloves J, Acosta MC, Gasull X, Belmonte C, Gallar J Pain 2016 157(2):399 https://doi.org/10.1097/j.pain.0000000000000455
- Lacosamide diminishes dryness-induced hyperexcitability of corneal cold sensitive nerve terminals Kovacs I, Dienes L, Perenyi K, Quirce S, Luna C, Mizerska K, Acosta MC, Belmonte C, Gallar J Eur J Pharmacol 2016 787:2 https://doi.org/10.1016/j.ejphar.2016.05.044
- Acid-sensing ion channels detect moderate acidifications to induce ocular pain Callejo G, Castellanos A, Castany M, Gual A, Luna C, Acosta MC, Gallar J, Giblin JP, Gasull X Pain 2015 156(3):483 https://doi.org/10.1097/01.j.pain.0000460335.49525.1-7
- Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus Dienes L, Kiss HJ, Perenyi K, Nagy ZZ, Acosta MC, Gallar J, Kovacs I PLoS One 2015 10(10):e0141621 https://doi.org/10.1371/journal.pone.0141621
- The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye Dienes L, Kiss HJ, Perenyi K, Szepessy Z, Nagy ZZ, Barsi A, Acosta MC, Gallar J, Kovacs I PLoS One 2015 10(8):e0135629 https://doi.org/10.1371/journal.pone.0135629
- What Causes Eye Pain? Belmonte C, Acosta MC, Merayo-Lloves J, Gallar J Curr Ophthalmol Rep 2015 3(2):111 https://doi.org/10.1007/s40135-015-0073-9
- Corneal Sensory Nerve Activity in an Experimental Model of UV Keratitis Acosta MC, Luna C, Quirce S, Belmonte C, Gallar J Invest Ophthalmol Vis Sci 2014 55(6):3403 https://doi.org/10.1167/iovs.13-13774
- Expression of Cholecystokinin, Gastrin, and Their Receptors in the Mouse Cornea Gonzalez-Coto AF, Alonso-Ron C, Alcalde I, Gallar J, Meana A, Merayo-Lloves J, Belmonte C Invest Ophthalmol Vis Sci 2014 55(3):1965 https://doi.org/10.1167/iovs.13-12068
- Preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule Sharif NA, Li L, Katoli P, Xu S, Veltman J, Li B, Scott D, Wax M, Gallar J, Acosta C, Belmonte C Exp Eye Res 2014 128:170 https://doi.org/10.1016/j.exer.2014.10.008
- Tear fluid hyperosmolality increases nerve impulse activity of cold thermoreceptor endings of the cornea Parra A, Gonzalez-Gonzalez O, Gallar J, Belmonte C Pain 2014 155(8):1481 https://doi.org/10.1016/j.pain.2014.04.025
- Changes in sensory activity of ocular surface sensory nerves during allergic keratoconjunctivitis Acosta MC, Luna C, Quirce S, Belmonte C, Gallar J Pain 2013 154(11):2353 https://doi.org/10.1016/j.pain.2013.07.012
- The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Neurobiology Stapleton F,Marfurt C, Golebiowski B, Rosenblatt M, Bereiter D, Begley C, Dartt D, Gallar J, Belmonte C, Hamrah P, Willcox M Invest Ophthalmol Vis Sci 2013 54(11):71 https://doi.org/10.1167/iovs.13-13226
- Regenerative Approaches as Alternatives to Donor Allografting for Restoration of Corneal Function Griffith M, Polisetti N, Kuffova L, Gallar J, Forrester J, Vemuganti G, Fuchsluger TA Ocul Surf 2012 10(3):170 https://doi.org/10.1016/j.jtos.2012.04.004.
- Cold Thermoreceptors, Unexpected Players in Tear Production and Ocular Dryness Sensations Belmonte C, Gallar J Invest Ophthalmol Vis Sci 2011 52(6):3888 https://doi.org/10.1167/iovs.09-5119
- Corneal Sensitivity in Diabetic Patients Subjected to Retinal Laser Photocoagulation Neira-Zalentein W, Holopainen JM, Tervo TM, Borras F, Acosta MC, Belmonte C, Gallar J Invest Ophthalmol Vis Sci 2011 52(8):6043 https://doi.org/10.1167/iovs.10-7054
- Methodological Considerations to Understand the Sensory Function of TRP Channels Meseguer VM, Denlinger BL, Talavera K Curr Pharm Biotechnol 2011 12(1):3
- Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea Parra A, Madrid R, Echevarria D, Del Olmo S, Morenilla-Palao C, Acosta MC, Gallar J, Dhaka A, Viana F, Belmonte C Nat Med 2010 16(12):1396 https://doi.org/10.1038/nm.2264
- Regeneration of functional nerves within full thickness collagen-phosphorylcholine corneal substitute implants in guinea pigs McLaughlin CR, Acosta MC, Luna C, Liu W, Belmonte C, Griffith M, Gallar J Biomaterials 2010 31(10):2770 https://doi.org/10.1016/j.biomaterials.2009.12.031
- Selective Changes in Human Corneal Sensation Associated with Herpes Simplex Virus Keratitis Gallar J, Tervo T, Neira W, Holopainen JM, Lamberg ME, Miñana F, Acosta MC, Belmonte C Invest Ophthalmol Vis Sci 2010 51(9):4516 https://doi.org/10.1167/iovs.10-5225
