A light against the loss of vision due to diabetes
DOI:
https://doi.org/10.22201/codeic.16076079e.2018.v19n5.a3Keywords:
diabetes, diabetic macular edema, Transient Receptor Potential Vanilloid 4 (TRPV4) ion channels, antagonists, therapeutic treatmentAbstract
Discovering innovative strategies for treatment of diabetic macular edema (DME) is a real challenge today. DME is a complication of type 1 and type 2 diabetes mellitus and the main cause of vision loss in patients suffering from diabetes. DME is characterized by increased permeability through the blood-retina barrier and hard exudate deposits in the central retina (the macula). The magnitude of the problem can be appreciated in view that 6.4 million of Mexican people have been diagnosed for diabetes, and 29% of them have DME. Here, we will describe the current treatment options for DME and their limitations, and we will also focus on the potential use of drugs that block Transient Receptor Potential Vanilloid 4 (TRPV4) ion channels. A recent study showed that blockade of TRPV4 by antagonist drugs abrogates the increased retinal permeability induced by diabetes, which is an alteration that promotes DME. In view that TRPV4 blockers are currently used in clinics to treat pulmonar edema, TRPV4 antagonists are expected to be used as curative agents for DME in the near future.
References
Amoaku, W. M., Saker, S. y Stewart, E. A. (2015). A review of therapies for diabetic macular oedema and rationale for combination therapy. Eye (Lond), 29(9), 1115-1130. DOI: https://doi.org/10.1038/eye.2015.110.
Arredondo Zamarripa, D., Noguez Imm, R., Bautista Cortes, A. M., Vazquez Ruiz, O., Bernardini, M., Fiorio Pla, A., . . . Thebault, S. (2017). Dual contribution of TRPV4 antagonism in the regulatory effect of vasoinhibins on blood-retinal barrier permeability: diabetic milieu makes a difference. Sci Rep, 7(1), 13094. DOI: https://doi.org/10.1038/s41598-017-13621-8.
Balakrishna, S., Song, W., Achanta, S., Doran, S. F., Liu, B., Kaelberer, M. M., . . . Jordt, S. E. (2014). TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury. Am J Physiol Lung Cell Mol Physiol, 307(2), L158-172. DOI: https://doi.org/10.1152/ajplung.00065.2014.
Bhagat, N., Grigorian, R. A., Tutela, A. y Zarbin, M. A. (2009). Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol, 54(1), 1-32. DOI: https://doi.org/10.1016/j.survophthal.2008.10.001.
Cheung, M., Bao, W., Behm, D. J., Brooks, C. A., Bury, M. J., Dowdell, S. E., . . . Thorneloe, K. S. (2017). Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. ACS Med Chem Lett, 8(5), 549-554. DOI: https://doi.org/10.1021/acsmedchemlett.7b00094.
Cioffi, D. L., Lowe, K., Alvarez, D. F., Barry, C. y Stevens, T. (2009). TRPing on the lung endothelium: calcium channels that regulate barrier function. Antioxid Redox Signal, 11(4), 765-776. DOI: https://doi.org/10.1089/ARS.2008.2221.
Corcóstegui Guraya, B. yMoreno Manresa, J. (2001). Capítulo 3. Edema macular diabético. Mesa Redonda, 77 Congreso de la Sociedad Española de Oftalmología, Barcelona, 2001, 37-51.
Gilliam, J. C. y Wensel, T. G. (2011). TRP channel gene expression in the mouse retina. Vision Res, 51(23-24), 2440-2452. DOI: https://doi.org/10.1016/j.visres.2011.10.009.
Grace, M. S., Bonvini, S. J., Belvisi, M. G. y McIntyre, P. (2017). Modulation of the TRPV4 ion channel as a therapeutic target for disease. Pharmacol Ther. DOI: https://doi.org/10.1016/j.pharmthera.2017.02.019.
Hamanaka, K., Jian, M. Y., Townsley, M. I., King, J. A., Liedtke, W., Weber, D. S., . . . Parker, J. C. (2010). TRPV4 channels augment macrophage activation and ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol, 299(3), L353-362. DOI: https://doi.org/10.1152/ajplung.00315.2009.
Hamanaka, K., Jian, M. Y., Weber, D. S., Alvarez, D. F., Townsley, M. I., Al-Mehdi, A. B., . . . Parker, J. C. (2007). TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs. Am J Physiol Lung Cell Mol Physiol, 293(4), L923-932. DOI: https://doi.org/10.1152/ajplung.00221.2007.
Hendrick, A. M., Gibson, M. V. y Kulshreshtha, A. (2015). Diabetic Retinopathy. Prim Care, 42(3), 451-464. DOI: https://doi.org/10.1016/j.pop.2015.05.005.
Jie, P., Tian, Y., Hong, Z., Li, L., Zhou, L., Chen, L. y Chen, L. (2015). Blockage of transient receptor potential vanilloid 4 inhibits brain edema in middle cerebral artery occlusion mice. Front Cell Neurosci, 9, 141. DOI: https://doi.org/10.3389/fncel.2015.00141.
Klein, B. E., Moss, S. E., Klein, R. y Surawicz, T. S. (1991). The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XIII. Relationship of serum cholesterol to retinopathy and hard exudate. Ophthalmology, 98(8), 1261-1265. Recuperado de: https://www.ncbi.nlm.nih.gov/pubmed/1923364.
Liedtke, W. y Friedman, J. M. (2003). Abnormal osmotic regulation in TRPV4-/- mice. Proc Natl Acad Sci U S A, 100(23), 13698-13703. DOI: https://doi.org/10.1073/pnas.1735416100.
Liedtke, W., Tobin, D. M., Bargmann, C. I. y Friedman, J. M. (2003). Mammalian TRPV4 (VR-OAC) directs behavioral responses to osmotic and mechanical stimuli in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 100 Suppl 2, 14531-14536. DOI: https://doi.org/10.1073/pnas.2235619100.
Lu, K. T., Huang, T. C., Tsai, Y. H. y Yang, Y. L. (2017). Transient receptor potential vanilloid type 4 channels mediate Na-K-Cl-co-transporter-induced brain edema after traumatic brain injury. J Neurochem, 140(5), 718-727. DOI: https://doi.org/10.1111/jnc.13920.
Monaghan, K., McNaughten, J., McGahon, M. K., Kelly, C., Kyle, D., Yong, P. H., . . . Curtis, T. M. (2015). Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium. PLoS One, 10(6), e0128359. DOI: https://doi.org/10.1371/journal.pone.0128359.
Morty, R. E. y Kuebler, W. M. (2014). TRPV4: an exciting new target to promote alveolocapillary barrier function. Am J Physiol Lung Cell Mol Physiol, 307(11), L817-821. DOI: https://doi.org/10.1152/ajplung.00254.2014.
Plant, T. D. y Strotmann, R. (2007). TRPV4. Handb Exp Pharmacol. (179), 189-205. DOI: https://doi.org/10.1007/978-3-540-34891-7_11.
Randhawa, P. K. y Jaggi, A. S. (2015). TRPV4 channels: physiological and pathological role in cardiovascular system. Basic Res Cardiol, 110(6), 54. DOI: https://doi.org/10.1007/s00395-015-0512-7.
Regnier, S., Malcolm, W., Allen, F., Wright, J. y Bezlyak, V. (2014). Efficacy of anti-VEGF and laser photocoagulation in the treatment of visual impairment due to diabetic macular edema: a systematic review and network meta-analysis. PLoS One, 9(7), e102309. DOI: https://doi.org/10.1371/journal.pone.0102309.
Reiter, B., Kraft, R., Gunzel, D., Zeissig, S., Schulzke, J. D., Fromm, M. y Harteneck, C. (2006). TRPV4-mediated regulation of epithelial permeability. FASEB J, 20(11), 1802-1812. DOI: https://doi.org/10.1096/fj.06-5772com.
Simonsen, U., Wandall-Frostholm, C., Olivan-Viguera, A. y Kohler, R. (2017). Emerging roles of calcium-activated K channels and TRPV4 channels in lung oedema and pulmonary circulatory collapse. Acta Physiol (Oxf), 219(1), 176-187. DOI: https://doi.org/10.1111/apha.12768.
Thebault, S. (2011). El epitelio pigmentario retiniano como componente de la barrera hemato-retiniana: implicación en la retinopatía diabética. Revista Digital Universitaria, 12(3). Recuperado de: http://www.revista.unam.mx/vol.12/num3/art31/index.html.
Thorneloe, K. S., Cheung, M., Bao, W., Alsaid, H., Lenhard, S., Jian, M. Y., . . . Willette, R. N. (2012). An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci Transl Med, 4(159), 159ra148. DOI: https://doi.org/10.1126/scitranslmed.3004276.
Vergnolle, N., Cenac, N., Altier, C., Cellars, L., Chapman, K., Zamponi, G. W., . . . Bunnett, N. W. (2010). A role for transient receptor potential vanilloid 4 in tonicity-induced neurogenic inflammation. Br J Pharmacol, 159(5), 1161-1173. DOI: https://doi.org/10.1111/j.1476-5381.2009.00590.x.
Vincent, F., Acevedo, A., Nguyen, M. T., Dourado, M., DeFalco, J., Gustafson, A., . . . Duncton, M. A. (2009). Identification and characterization of novel TRPV4 modulators. Biochem Biophys Res Commun, 389(3), 490-494. DOI: https://doi.org/10.1016/j.bbrc.2009.09.007.
Wang, J. K., Huang, T. L., Su, P. Y. y Chang, P. Y. (2015). An updated review of long-term outcomes from randomized controlled trials in approved pharmaceuticals for diabetic macular edema. Eye Sci, 30(4), 176-183. Recuperado de: http://ykxb.amegroups.com/article/view/3523/4246.
Watanabe, H., Davis, J. B., Smart, D., Jerman, J. C., Smith, G. D., Hayes, P., . . . Nilius, B. (2002). Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. J Biol Chem, 277(16), 13569-13577. DOI: https://doi.org/10.1074/jbc.M200062200.
Willette, R. N., Bao, W., Nerurkar, S., Yue, T. L., Doe, C. P., Stankus, G., . . . Xu, X. (2008). Systemic activation of the transient receptor potential vanilloid subtype 4 channel causes endothelial failure and circulatory collapse: Part 2. J Pharmacol Exp Ther, 326(2), 443-452. DOI: https://doi.org/10.1124/jpet.107.134551.
Wu, S., Jian, M. Y., Xu, Y. C., Zhou, C., Al-Mehdi, A. B., Liedtke, W., . . . Townsley, M. I. (2009). Ca2+ entry via alpha1G and TRPV4 channels differentially regulates surface expression of P-selectin and barrier integrity in pulmonary capillary endothelium. Am J Physiol Lung Cell Mol Physiol, 297(4), L650-657. DOI: https://doi.org/10.1152/ajplung.00015.2009.
Yau, J. W., Rogers, S. L., Kawasaki, R., Lamoureux, E. L., Kowalski, J. W., Bek, T., . . . Meta-Analysis for Eye Disease Study, G. (2012). Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care, 35(3), 556-564. DOI: https://doi.org/10.2337/dc11-1909.
Yin, J., Hoffmann, J., Kaestle, S. M., Neye, N., Wang, L., Baeurle, J., . . . Kuebler, W. M. (2008). Negative-feedback loop attenuates hydrostatic lung edema via a cGMP-dependent regulation of transient receptor potential vanilloid 4. Circ Res, 102(8), 966-974. DOI: https://doi.org/10.1161/CIRCRESAHA.107.168724.
Yin, J., Michalick, L., Tang, C., Tabuchi, A., Goldenberg, N., Dan, Q., . . . Kuebler, W. M. (2016). Role of Transient Receptor Potential Vanilloid 4 in Neutrophil Activation and Acute Lung Injury. Am J Respir Cell Mol Biol, 54(3), 370-383. DOI: https://doi.org/10.1165/rcmb.2014-0225OC.
Zhang, X., Zeng, H., Bao, S., Wang, N., & Gillies, M. C. (2014). Diabetic macular edema: new concepts in patho-physiology and treatment. Cell Biosci, 4, 27. DOI: https://doi.org/10.1186/2045-3701-4-27.
Zhao, D., Nguyen, C. T., Wong, V. H., Lim, J. K., He, Z., Jobling, A. I., . . . Bui, B. V. (2017). Characterization of the Circumlimbal Suture Model of Chronic IOP Elevation in Mice and Assessment of Changes in Gene Expression of Stretch Sensitive Channels. Front Neurosci, 11, 41. DOI: https://doi.org/10.3389/fnins.2017.00041.
Zhao, P. Y., Gan, G., Peng, S., Wang, S. B., Chen, B., Adelman, R. A., & Rizzolo, L. J. (2015). TRP Channels Localize to Subdomains of the Apical Plasma Membrane in Human Fetal Retinal Pigment Epithelium. Invest Ophthalmol Vis Sci, 56(3), 1916-1923. DOI: https://doi.org/10.1167/iovs.14-15738.
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Revista Digital Universitaria es editada por la Universidad Nacional Autónoma de México se distribuye bajo una Licencia Creative Commons Atribución-NoComercial 4.0 Internacional. Basada en una obra en http://revista.unam.mx/.
