Topical Timolol Inhibits Corneal Neovascularization in Rabbits
Medical hypothesis discovery and innovation in ophthalmology,
Vol. 6 No. 2 (2017),
1 June 2017
Abstract
Timolol is a non-selective beta-adrenergic antagonist that is similar to propranolol. The mechanism through which these drugs act on the regression of neovascularization is largely unknown. However, it is thought that the drugs may act through vascular endothelial growth factor signaling, vasoconstriction, and vascular endothelial cell apoptosis. The aim of this study was to determine the effect of timolol on corneal neovascularization in rabbits. Neovascularization was induced in the eyes of 20 rabbits. Next, the rabbits were divided into two groups: the timolol (experimental) group received eye drops containing timolol 0.5% twice per day; and the saline (control) group received saline drops twice per day for two weeks. After 7 days, the mean area of corneal neovascularization (presented as a percentage relative to baseline) was significantly lower in the timolol group than in the saline group (4.63 ± 4.61% versus 58.39 ± 6.31%, P < 0.001). After 2 weeks, the mean area of corneal neovascularization was 0.85 ± 1.33% in the timolol group and 1.73 ± 2.06% in the saline group (P = 0.315). After the first week of treatment, timolol significantly reduced the area of neovascularization compared to control. Timolol may increase the rate of recovery from corneal neovascularization.ÂReferences
Krachmer MJ, Mannis EJ. Cornea, fundamental, diagnosis and management: Mosby Elsevier; 2008.
Chang JH, Gabison EE, Kato T, Azar DT. Corneal neovascularization. Curr Opin Ophthalmol. 2001;12(4):242-9. DOI: 10.1097/00055735-20010800 0-00002 PMID: 11507336
DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37(3):588-98. DOI: 10.1016/j.jcrs.2010.12.037 PMID: 21333881
Perez-Santonja JJ, Campos-Mollo E, Lledo-Riquelme M, Javaloy J, Alio JL. Inhibition of corneal neovascularization by topical bevacizumab (Anti-VEGF) and Sunitinib (Anti-VEGF and Anti-PDGF) in an animal model. Am J Ophthalmol. 2010;150(4):519-28 e1. DOI: 10.1016/j.ajo.2010.04.024 PMID: 20591397
Perez-Santonja JJ, Campos-Mollo E, Lledo-Riquelme M, Fernandez-Sanchez L, Cuenca-Navarro N. [Vascular morphological and microdensity changes of corneal neovascularization induced by topical bevacizumab and sunitinib in an animal model]. Arch Soc Esp Oftalmol. 2013;88(12):473-81. DOI: 10.1016/j.oftal. 2013.07.007 PMID: 24257257
Tunik S, Nergiz Y, Keklikci U, Akkus M. The subconjunctival use of cetuximab and bevacizumab in inhibition of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol. 2012;250(8):1161-7. DOI: 10.1007/s0 0417-012-2008-6 PMID: 22527313
Stevenson W, Cheng SF, Dastjerdi MH, Ferrari G, Dana R. Corneal neovascularization and the utility of topical VEGF inhibition: ranibizumab (Lucentis) vs bevacizumab (Avastin). Ocul Surf. 2012;10(2):67-83. DOI: 10.1016/j.jtos.2012.01.005 PMID: 22482468
Akar EE, Oner V, Kucukerdonmez C, Aydin Akova Y. Comparison of subconjunctivally injected bevacizumab, ranibizumab, and pegaptanib for inhibition of corneal neovascularization in a rat model. Int J Ophthalmol. 2013;6(2):136-40. DOI: 10.3980/j.issn.2222-3959.2013.02.05 PMID: 236384 11
Ristori C, Filippi L, Dal Monte M, Martini D, Cammalleri M, Fortunato P, et al. Role of the adrenergic system in a mouse model of oxygen-induced retinopathy: antiangiogenic effects of beta-adrenoreceptor blockade. Invest Ophthalmol Vis Sci. 2011;52(1):155-70. DOI: 10.1167/iovs.10-5536 PMID: 20739470
Haider KM, Plager DA, Neely DE, Eikenberry J, Haggstrom A. Outpatient treatment of periocular infantile hemangiomas with oral propranolol. J AAPOS. 2010;14(3):251-6. DOI: 10.1016/j.jaapos.2010.05.002 PMID: 20603059
Guo S, Ni N. Topical treatment for capillary hemangioma of the eyelid using beta-blocker solution. Arch Ophthalmol. 2010;128(2):255-6. DOI: 10.1001/ar chophthalmol.2009.370 PMID: 20142555
Xue K, Hildebrand GD. Deep periocular infantile capillary hemangiomas responding to topical application of timolol maleate, 0.5%, drops. JAMA Ophthalmol. 2013;131(9):1246-8. DOI: 10.1001/jama ophthalmol.2013.4171 PMID: 23846584
McMahon P, Oza V, Frieden IJ. Topical timolol for infantile hemangiomas: putting a note of caution in "cautiously optimistic". Pediatr Dermatol. 2012;29(1):127-30. DOI: 10.1111/j.1525-1470.2011.0 1685.x PMID: 22256996
Ciudad Blanco C, Campos Dominguez M, Moreno Garcia B, Villanueva Alvarez-Santullano CA, Berenguer Frohner B, Suarez Fernandez R. Episcleral infantile hemangioma successfully treated with topical timolol. Dermatol Ther. 2015;28(1):22-4. DOI: 10.1111/dth.12 173 PMID: 25286087
Chim H, Armijo BS, Miller E, Gliniak C, Serret MA, Gosain AK. Propranolol induces regression of hemangioma cells through HIF-1alpha-mediated inhibition of VEGF-A. Ann Surg. 2012;256(1):146-56. DOI: 10.1097/SLA.0b013e318254ce7a PMID: 22580 939
Ji Y, Chen S, Li K, Xiao X, Zheng S, Xu T. The role of beta-adrenergic receptor signaling in the proliferation of hemangioma-derived endothelial cells. Cell Div. 2013;8(1):1. DOI: 10.1186/1747-1028-8-1 PMID: 2328 6511
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671-5. DOI: 10.1038/nmeth.2089 PMID: 22930834
Kim TI, Kim SW, Kim S, Kim T, Kim EK. Inhibition of experimental corneal neovascularization by using subconjunctival injection of bevacizumab (Avastin). Cornea. 2008;27(3):349-52. DOI: 10.1097/ICO.0b013e 31815cf67d PMID: 18362666
Oner V, Kucukerdonmez C, Akova YA, Colak A, Karalezli A. Topical and subconjunctival bevacizumab for corneal neovascularization in an experimental rat model. Ophthalmic Res. 2012;48(3):118-23. DOI: 10.1159/000337139 PMID: 22538642
Simavli H, Erdurmus M, Terzi EH, Bucak YY, Onder HI, Kukner AS. The effect of beta receptor blockade through propranolol on corneal neovascularization. J Ocul Pharmacol Ther. 2014;30(8):650-6. DOI: 10.1089/jop.2013.0238 PMID: 24983781
Schwartz S, George J, Ben-Shoshan J, Luboshits G, Avni I, Levkovitch-Verbin H, et al. Drug modification of angiogenesis in a rat cornea model. Invest Ophthalmol Vis Sci. 2008;49(1):250-4. DOI: 10.1167/iovs.06-1337 PMID: 18172099
- Abstract Viewed: 1989 times
- Full Text PDF Downloaded: 1371 times