Evaluar el efecto del genipin sobre la cabeza del nervio óptico, en un modelo animal de glaucoma

dc.contributor.advisorÁvila Castañeda, Marcel Yecidspa
dc.contributor.advisorDueñas Gómez, Zulma Janethspa
dc.contributor.authorCórdoba Ortega, Carlos Miguelspa
dc.contributor.researchgroupCiencias Básicas y Clínicas en Oftalmologíaspa
dc.date.accessioned2021-01-14T14:44:58Zspa
dc.date.available2021-01-14T14:44:58Zspa
dc.date.issued2021-01-13spa
dc.description.abstractPurpose: Crosslinking of the collagen of the lamina cribrosa and the peripapillary sclera could be a plausible method to modulate biomechanical stress and strain-based injuries in the laminar region caused by glaucoma. Method: 32 albino Wistar rats distributed in 4 groups, the right eyes were infiltrated via retrobulbar with genipin (15 mM and 150 mcl), BAPN (beta-aminopropionitrile) (10 mM and 150mcl). The left eyes were used as controls. Immediate and weekly IOP measurements were made for 1 month with the Tonolab rebound tonometer. Immunohistochemistry was performed for the S-100 protein and GFAP, to measure the change in the length of the optic nerve and the degree of transport blockage in ONH. Finally, the molecular changes were analyzed using the real-time polymerase chain reaction (RT-PCR). Results: Genipin did not affect IOP or optic nerve head morphology, BAPN significantly reduced IOP in all treatment groups. The cup / disc ratio in glaucomatous eyes had increased to approximately 0.6 compared to 0.3 in controls. Axial length was more pronounced in BAPN-treated eyes. Finally, we did not observe any change in gene expression in the treatments. Conclusion: Crosslinking with genipin in rats avoids biomechanical deformation of the peripapillary sclera, has an anti-inflammatory and neuroprotective effect, we did not observe signs of toxicity when evaluating axons, RGCs and macroscopic anatomy of the eyes after retrobulbar injection of genipin. nor from BAPN.spa
dc.description.abstractPropósito: La reticulación del colágeno de la lámina cribosa y la esclera peripapilar, podría ser un método plausible para modular el estrés biomecánico y las lesiones basados en la tensión en la región laminar causados por el gluacoma. Método: 32 ratas wistar albinas distribuidas en 4 grupos, los ojos derechos se infiltraron vía retrobulbar con genipin (15 mM y 150 mcl), BAPN (beta – aminopropilnitrilo) (10 mM y 150mcl). Los ojos izquierdos se usaron como controles. Se realizarón mediciones de la PIO inmediatas y semanales durante 1 mes con el tonómetro de rebote Tonolab. Se realizó inmunohistoquímica para la proteína S-100 y GFAP, para medir el cambio en la longitud del nervio óptico y el grado de bloqueo del transporte en la cabeza del nervio óptico. Finalmente, los cambios moleculares se analizaron mediante la reacción en cadena de la polimerasa en tiempo real (RT-PCR). Resultados: Genipin no afectó la PIO ni la morfología de la cabeza del nervio óptico,en cambio, el BAPN redujo significativamente la PIO en todos los grupos de tratamiento. La relación copa / disco en ojos glaucomatosos había aumentado aproximadamente 0,6 en comparación con 0,3 en los controles. La longitud axial fue más pronunciada en los ojos tratados con BAPN. Por último, no observamos ningún cambio en la expresión de genes en los tratamientos. Conclusión: La reticulación con genipin en ratas evita la deformación biomecánica la esclera peripapilar, tiene un efecto antiinflamatorio y neuroprotector, no observamos signos de toxicidad al evaluar los axones, las CGR y la anatomía macroscópica de los ojos después de la inyección retrobulbar de genipin ni de BAPN.spa
dc.description.additionalLínea de Investigación: Glaucoma, estudio experimental en un modelo animalspa
dc.description.degreelevelEspecialidades Médicasspa
dc.format.extent48spa
dc.format.mimetypeapplication/pdfspa
dc.identifier.citationCordoba-Ortega Carlos (2021). Evaluar el efecto del genipin sobre el complejo del nervio óptico en un modelo animal de glaucoma (Tesis especialidad médica). Universidad Nacional de Colombia, Bogotá.spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/78732
dc.language.isospaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.programBogotá - Medicina - Especialidad en Oftalmologíaspa
dc.relation.references1. Parihar JK. Glaucoma: The 'Black hole' of irreversible blindness. Med J Armed Forces India. 2016; 72(1):3–4. doi:10.1016/j.mjafi.2015.12.001spa
dc.relation.references2. Anderson, Douglas R. “Normal-tension glaucoma (Low-tension glaucoma).” Indian journal of ophthalmology vol. 59 Suppl, Suppl1 (2011): S97-101. doi:10.4103/0301-4738.73695spa
dc.relation.references3. Miglior S, Zeyen T, Pfeiffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology. 2005; 112(3): 366-375. doi:10.1016/j.ophtha.2004.11.030spa
dc.relation.references4. Miglior S, Zeyen T, Pfeiffer N, Cunha-Vaz J, Torri V, Adamsons, European Glaucoma Prevention Study Group. The European glaucoma prevention study design and baseline description of the participants. Ophthalmology. 2002; 109 (9):1612-1621. doi:10.1016/s0161-6420(02)01167-3spa
dc.relation.references5. Wong V, Bui B, Vingrys A. Clinical and experimental links between diabetes and glaucoma, Clinical & experimental optometry: journal of the Australian Optometrical Association. 2010;91(1):4-23. https://doi.org/10.1111/j.1444-0938.2010.00546.xspa
dc.relation.references6. Shih KC, Lam KS, Tong L. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutr Diabetes. 2017;7(3):e251. Published 2017 Mar 20. doi:10.1038/nutd.2017.4spa
dc.relation.references7. Nakamura M, Kanamori A, Negi A. Diabetes mellitus as a risk factor for glaucomatous optic neuropathy. Ophthalmologica. 2005;219(1):1-10. doi:10.1159/000081775spa
dc.relation.references8. Campbell IC, Hannon BG, Read AT, Sherwood JM, Schwaner SA, Ethier CR. Quantification of the efficacy of collagen cross-linking agents to induce stiffening of rat sclera [published correction appears in J R Soc Interface. 2017 May;14 (130):]. J R Soc Interface. 2017;14(129):20170014. doi:10.1098/rsif.2017.0014spa
dc.relation.references9. Koriyama Y, Takagi Y, Chiba K, Yamazaki M, Sugitani K, et al. (2013) Requirement of Retinoic Acid Receptor b for Genipin Derivative-Induced Optic Nerve Regeneration in Adult Rat Retina. PLoS ONE 8(8): e71252. doi: 10.1371/journal.pone.0071252spa
dc.relation.references10. Rijt SV, Habibovic P. Enhancing regenerative approaches with nanoparticles. J R Soc Interface. 2017 Apr; 14(129): 20170014, Published online 2017 Apr 5. Doi 10.1098/rsif.2017.0014spa
dc.relation.references11. Phulke S, Kaushik S, Kaur S, Pandav SS. Steroid-induced Glaucoma: An Avoidable Irreversible Blindness. J Curr Glaucoma Pract. 2017;11(2):67-72. doi:10.5005/jp-journals-l0028-1226spa
dc.relation.references12. Shin JK, Lee SM. Genipin protects the liver from ischemia/reperfusion injury by modulating mitochondrial quality control. Toxicol Appl Pharmacol. 2017;328:25-33. doi:10.1016/j.taap.2017.05.002spa
dc.relation.references13. Avila MY, Gerena VA, Navia JL. Corneal crosslinking with genipin, comparison with UV-riboflavin in ex-vivo model. Mol Vis. 2012;18:1068-1073.spa
dc.relation.references14. Pijanka JK, Coudrillier B, Ziegler K, Sorensen T, Meek KM, Nguyen TD, Quigley HA, Boote C: Quantitative mapping of collagen fiber orientation in non-glaucoma and glaucoma posterior human sclerae. Invest Ophthalmol Vis Sci 2012, 53:5258-5270.spa
dc.relation.references15. Girard MJ, Dahlmann-Noor A, Rayapureddi S, Bechara JA, Bertin BM, Jones H, Albon J, Khaw PT, Ethier CR: Quantitative mapping of scleral fiber orientation in normal rat eyes. Invest Ophthalmol Vis Sci 2011, 52:9684-9693.spa
dc.relation.references16. Hannon BG, Luna C, Feola AJ, et al. Assessment of Visual and Retinal Function Following In Vivo Genipin-Induced Scleral Crosslinking. Transl Vis Sci Technol. 2020;9(10):8. Published 2020 Sep 8. doi:10.1167/tvst.9.10.8spa
dc.relation.references17. Strouthidis NG, Girard MJ. Altering the way, the optic nerve head responds to intraocular pressure-a potential approach to glaucoma therapy. Curr Opin Pharmacol. 2013;13(1):83-89. doi:10.1016/j.coph.2012.09.001spa
dc.relation.references18. Beidoe G, Mousa SA. Current primary open-angle glaucoma treatments and future directions. Clin Ophthalmol. 2012;6:1699-1707. doi:10.2147/OPTH.S32933spa
dc.relation.references19. Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma: A Review. JAMA.2014; 311(18):1901–1911. doi:10.1001/jama.2014.3192spa
dc.relation.references20. Mantravadi AV, Vadhar N. Glaucoma. Prim Care. 2015;42(3):437-449. doi: 10.1016/j.pop.2015.05.008spa
dc.relation.references21. E. Kim and R. Varma, “Glaucoma in Latinos/Hispanics.,” Curr. Opin. Ophthalmol., vol. 21, no. 2, pp. 100–105, 2010.spa
dc.relation.references22. Alm A. Latanoprost in the treatment of glaucoma. Clin Ophthalmol. 2014; 8:1967-1985https://doi.org/10.2147/OPTH.S59162spa
dc.relation.references23. Girard MJ, Suh JK, Bottlang M, Burgoyne CF, Downs JC. Biomechanical changes in the sclera of monkey eyes exposed to chronic IOP elevations. Invest Ophthalmol Vis Sci. 2011; 52: 5656–5669.spa
dc.relation.references24. H. A. Quigley, “Number of people with glaucoma worldwide.,” Br. J. Ophthalmol., vol. 80, no. 5, pp. 389–393, 1996.spa
dc.relation.references25. Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma: AReview. JAMA.2014;311(18):1901–1911. doi:10.1001/jama.2014.3192spa
dc.relation.references26. Girard MJ, Dahlmann-Noor A, Rayapureddi S, Bechara JA, Bertin BM, Jones H, Albon J, Khaw PT, Ethier CR: Quantitative mapping of scleral fiber orientation in normal rat eyes. Invest Ophthalmol Vis Sci 2011, 52:9684-9693.spa
dc.relation.references27. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-267. doi:10.1136/bjo.2005.081224spa
dc.relation.references28. Prevalencia de glaucoma y factores de riesgo asociados en una población de adultos mayores de 50 años de bajos recursos económicos en el nororiente de Colombia. Juan Carlos Rueda. 2005.spa
dc.relation.references29. Cuellar Saenz, Z. La Ceguera. Un compromiso de todos. Medicina. 2003. 24(3), 188-196. Recuperado a partir de https://revistamedicina.net/ojsanm/index.php/Medicina/article/view/60-3spa
dc.relation.references30. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86(2):238-242. doi:10.1136/bjo.86.2.238spa
dc.relation.references31. Cuellar Saenz. Ceguera y pobreza en el siglo XXI .Cuadernos de medicina en investigación y salud. Año 1, Vol 1- Número 3 - Dic 2007spa
dc.relation.references32. Thornton IL, Dupps WJ, Sinha Roy A, Krueger RR. Biomechanical effects of intraocular pressure elevation on optic nerve/lamina cribrosa before and after peripapillary scleral collagen cross-linking. Invest Ophthalmol Vis Sci. 2009;50(3):1227-1233. doi:10.1167/iovs.08-1960spa
dc.relation.references33. Y. C. Tham, X. Li, T. Y. Wong, H. A. Quigley, T. Aung, and C. Y. Cheng. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology. 2014.(121)11:2081–2090. doi.org/10.1016/j.ophtha.2014.05.013spa
dc.relation.references34. Ma Y, Pavlatos E, Clayson K, Pan X, Kwok S, Sandwisch T, Liu J. Mechanical Deformation of Human Optic Nerve Head and Peripapillary Tissue in Response to Acute IOP Elevation. Investigative Ophthalmology & Visual Science.2019 (60): 913-920. doi:10.1167/iovs.18-26071spa
dc.relation.references35. Campbell IC, Coudrillier B, Mensah J, Abel RL, Ethier CR. Automated segmentation of the lamina cribrosa using Frangi’s filter: a novel approach for rapid identification of tissue volume fraction and beam orientation in a trabeculated structure in the eye. J. R. Soc. Interface. 2015;12spa
dc.relation.references36. Kimball E, Nguyen C, Steinhart MR, Nguyen, TD, Pease M, Oglesby EN,Oveson BC, Quigley HA. Experimental scleral cross-linking increases glaucoma damage in a mouse model. Experimental Eye Research. 2014. 128:129-140. https://doi.org/10.1016/j.exer.2014.08.016.spa
dc.relation.references37. Korneva A, Nguyen C, Schaub J, Nguyen T, Quigley H. Biomechanical effects on the mouse optic nerve head in experimental scleral crosslinking in glaucoma. Investigative Ophthalmology & Visual Science. 2019.spa
dc.relation.references38. Yang, YF., Sun, Y., Acott, T. et al. Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells. Sci Rep 6, 30505 (2016). https://doi.org/10.1038/srep30505spa
dc.relation.references39. Denlinger D, Keates RH. Effect of beta-aminopropionitrile (BAPN) on corneal wound strength. Ann Ophthalmol. 1984;16(7):625-627spa
dc.relation.references40. Tehrani S, Delf RK, Cepurna WO, Davis L, Johnson EC, Morrison JC. In Vivo Small Molecule Delivery to the Optic Nerve in a Rodent Model. Sci Rep. 2018;8(1):4453. Published 2018 Mar 13. doi:10.1038/s41598-018-22737-4spa
dc.relation.references41. American Academy of Ophtptamology. Section 6: Glaucoma. 2012spa
dc.relation.references42. Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol. 2002;86(2):238-242. doi:10.1136/bjo.86.2.238spa
dc.relation.references43. Cheng JW, Wei RL. Meta-analysis of 13 randomized controlled trials comparing bimatoprost with latanoprost in patients with elevated intraocular pressure. Clin Ther. 2008;30(4):622-632. doi:10.1016/j.clinthera.2008.04.006spa
dc.relation.references44. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11):2081-2090. doi:10.1016/j.ophtha.2014.05.013spa
dc.relation.references45. H. A. Quigley, “Number of people with glaucoma worldwide.,” Br. J. Ophthalmol., vol. 80, no. 5, pp. 389–393, 1996.spa
dc.relation.references46. H. A. Quigley and A. T. Broman, “The number of people with glaucoma worldwide in 2010 and 2020.,” Br. J. Ophthalmol., vol. 90, no. 3, pp. 262–7, 2006spa
dc.relation.references47. Prevalencia de glaucoma y factores de riesgo asociados en una población de adultos mayores de 50 años de bajos recursos económicos en el nororiente de Colombia. Juan Carlos Rueda. 2005.spa
dc.relation.references48. Dare E, V, Griffith M, Poitras P, Kaupp J, A, Waldman S, D, Carlsson D, J, Dervin G, Mayoux C, Hincke M, T: Genipin Cross-Linked Fibrin Hydrogels for in vitro Human Articular Cartilage Tissue-Engineered Regeneration. Cells Tissues Organs 2009; 190:313-325. doi: 10.1159/000209230spa
dc.relation.references49. Zhou X. Wang J, Fang W, Ta Y, Zhao T, Xia J, Liang C. Hua J, Li F, Chen Q. Genipin cross-linked type II collagen/chondroitin sulfate composite hydrogel-like cell delivery system induces differentiation of adipose-derived stem cells and regenerates degenerated nucleus pulposus. Acta Biomaterialia. 2018. 71: 496-509.spa
dc.relation.references50. Hannon, BG, Schwaner SA, Boazak EM, Gerberich BG, Winger EJ, Prausnitz, MR, Ethier CR. Sustained scleral stiffening in rats after a single genipin treatment. Journal of the Royal Society. (2019)16(159). https://doi.org/10.1098/rsif.2019.0427spa
dc.relation.references51. Paul, A., Cantor, A., Shum-Tim, D. et al. Superior Cell Delivery Features of Genipin Crosslinked Polymeric Microcapsules: Preparation, In Vitro Characterization and Pro-Angiogenic Applications Using Human Adipose Stem Cells. Mol Biotechnol 48, 116–127 (2011). https://doi.org/10.1007/s12033-010-9352-8spa
dc.relation.references52. Coudrillier B, Campbell IC, Read AT, et al. Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa. Invest Ophthalmol Vis Sci. 2016;57(6):2666-2677. doi:10.1167/iovs.15-18193spa
dc.relation.references53. Campbell IC, Hannon BG, Read AT, Sherwood JM, Schwaner SA, Ethier CR. 2017 Quantification of the efficacy of collagen cross-linking agents to induce stiffening of rat sclera. J. R. Soc. Interface 14: 20170014. http://dx.doi.org/10.1098/rsif.2017.0014spa
dc.relation.references54. Liu H, Flanagan J. A Mouse Model of Chronic Ocular Hypertension Induced by Circumlimbal Suture Invest. Ophthalmol. Vis. Sci. 2017; 58(1):353-361. doi:10.1167/iovs.16-20576spa
dc.relation.references55. H. He Z, Zhao D, van Koeverden AK, et al. A Model of Glaucoma Induced by Circumlimbal Suture in Rats and Mice. J Vis Exp. 2018;(140):58287. Published 2018 Oct 5. doi:10.3791/58287spa
dc.relation.references56. Quigley HA, McKinnon SJ, Zack DJ, et al. Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats. Invest Ophthalmol Vis Sci. 2000; 41(11):3460-3466spa
dc.relation.references57. Moorhead LC, Smith J, Stewart R, Kimbrough R. Effects of beta-aminopropionitrile after glaucoma filtration surgery: pilot human trial. Ann Ophthalmol. 1987;19(6):223-225.spa
dc.relation.references58. Koo HJ, Song YS, Kim HJ, et al. Anti-inflammatory effects of genipin, an active principle of gardenia. Eur J Pharmacol. 2004;495(2-3):201-208. doi:10.1016/j.ejphar.2004.05.0spa
dc.relation.references59. Wang, A Ray, K Rodgers, et al. Global Gene Expression Changes in Rat Retinal Ganglion Cells in Experimental Glaucoma. Investigative Ophthalmology & Visual Science August 2010, Vol.51, 4084-4095. doi.org/10.1167/iovs.09-4864spa
dc.rightsDerechos reservados - Universidad Nacional de Colombiaspa
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.rights.spaAcceso abiertospa
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.ddc610 - Medicina y saludspa
dc.subject.proposalGlaucomaspa
dc.subject.proposalGlaucomaeng
dc.subject.proposalGenipineng
dc.subject.proposalGenipinspa
dc.subject.proposalBAPNspa
dc.subject.proposalBAPNeng
dc.subject.proposalRGCeng
dc.subject.proposalRGCspa
dc.subject.proposalPIOspa
dc.subject.proposalIOPeng
dc.titleEvaluar el efecto del genipin sobre la cabeza del nervio óptico, en un modelo animal de glaucomaspa
dc.title.alternativeTo evaluate the effect of the genipin on the head of the optic nerve, in an animal model of glaucomaspa
dc.typeTrabajo de grado - Especialidad Médicaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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