Effect of Various Topical Therapies on Intraocular Pressure in a Rat Model of Corneal Haze

Document Type : Original Article

Authors
Negin Rahimdoust Mozhdehi 1
Samaneh Ghasemi 1
Rahim Saffari 2
Hanieh Shaterzadeh Yazdi 3
Hossein Kazemi Mehrjerdi 4
1 Department of Clinical Sciences, Faculty of Veterinary .Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
2 Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
3 .Private veterinary pathologist, Mashhad, Iran
4 Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
10.61882/eltiamj.12.1.10
Abstract
Background: Corneal opacity is a major cause of vision impairment resulting from trauma and wounds. Corticosteroids are effective in reducing fibrosis; however, their use is associated with an increased risk of intraocular pressure (IOP). Losartan, an angiotensin II antagonist and TGF-β pathway inhibitor, has demonstrated antifibrotic potential in topical applications; however, its safety regarding IOP changes in animal models remains unclear.
Objectives: This study aimed to evaluate the effects of topical losartan, betamethasone, and their combination on IOP in a rat model of partial-thickness corneal injury over a four-week treatment period.
Methods: Twenty-four adult male Wistar rats were randomly assigned to four groups (n=6): negative control (BSS), topical Losartan (0.08%), topical betamethasone (0.1%), and a combination of losartan + betamethasone. Partial-thickness corneal injury was induced on day 0, and treatments were administered from day 4 onward. Each treatment consisted of six daily doses (every two hours) applied to the right eye for 30 days. At the end of the study, IOP in both eyes was measured using an iCare tonometer in three sets of six readings (a total average of 18 readings per eye). Data were reported as mean ± standard deviation and analyzed statistically for comparisons between groups and between treated and untreated eyes.
Results: Mean IOP across the losartan, betamethasone, combination, and control groups showed no significant differences (p > 0.05). Similarly, no significant differences were observed between the treated (right) and untreated (left) eyes within any group (p > 0.05).
Conclusions
This study demonstrated that one-month application of topical Losartan, Betamethasone, and their combination for the treatment of opacity caused by partial-thickness corneal injury in rats has no significant impact on intraocular pressure.

Keywords

Subjects

1.       Yang S, Zhang J, Tan Y, Wang Y. Unraveling the mechanobiology of cornea: From bench side to the clinic. Front Bioeng Biotechnol. 2022;10(October):1–17.
2.       Barrientez B, Nicholas SE, Whelchel A, Sharif R, Hjortdal J, Karamichos D. Corneal injury: Clinical and molecular aspects. Exp Eye Res [Internet]. 2019 Sep;186:107709. Available from: https://doi.org/10.1016/j.exer.2019.107709
3.       Wilson SE, Sampaio LP, Shiju TM, Hilgert GSL, de Oliveira RC. Corneal Opacity: Cell Biological Determinants of the Transition From Transparency to Transient Haze to Scarring Fibrosis, and Resolution, After Injury. Investig Ophthalmol Vis Sci. 2022;63(1):1–12.
4.       Yavuz Ü, Yener K, Hayat A. Eye Cases Requiring Emergency Intervention in Animals *. 2020;9(1):90–7.
5.       Nassiri N, Latifi Z, Nassiri S, Azemati A, Rezaeyeh AP, Kavousnezhad S, et al. The Effect of Topical Betamethasone Eye Drops on Postoperative Haze among Patients Undergoing Corneal Collagen Cross-Linking: a Randomized, Double Blind Placebo Controlled Study. J Ophthalmic Optom Sci. 2018;2(2):17–24.
6.       Tani E. Effects of Various Eye Drops on Corneal Wound Healing after Superficial Keratectomy in Rabbits. Jpn J Ophthalmol [Internet]. 2002 Oct;46(5):488–95. Available from: http://journals.lww.com/00003226-200612000-00010
7.       Sato K, Nishiguchi KM, Maruyama K, Moritoh S, Fujita K, Ikuta Y, et al. Topical ocular dexamethasone decreases intraocular pressure and body weight in rats. J Negat Results Biomed [Internet]. 2016 Dec 12;15(1):5. Available from: http://jnrbm.biomedcentral.com/articles/10.1186/s12952-016-0048-x
8.       Hashizume N, Saika S, Okada Y, Miyamoto T, Shimizu K, Ohnishi Y. Effects of antiinflammatory drugs on migration of the rabbit corneal epithelium. J Cataract Refract Surg [Internet]. 2001 Sep;27(9):1499–502. Available from: https://journals.lww.com/02158034-200109000-00039
9.       Sarchahi AA, Maimandi A, Khodakaram Tafti A, Amani M. Effects of Acetylcysteine and Dexamethasone on Experimental Corneal Wounds in Rabbits. Ophthalmic Res [Internet]. 2008;40(1):41–8. Available from: https://karger.com/ORE/article/doi/10.1159/000111158
10.   Trujillo Cubillo L, Gurdal M, Zeugolis DI. Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines. Adv Drug Deliv Rev. 2024;209(February).
11.   Pereira-Souza AL, Ambrósio R, Bandeira F, Salomão MQ, Souza Lima A, Wilson SE. Topical Losartan for Treating Corneal Fibrosis (Haze): First Clinical Experience. J Refract Surg [Internet]. 2022 Nov;38(11):741–6. Available from: https://journals.healio.com/doi/10.3928/1081597X-20221018-02
12.   Sampaio LP, Hilgert GSL, Shiju TM, Santhiago MR, Wilson SE. Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury. Transl Vis Sci Technol [Internet]. 2022 Jul 12;11(7):9. Available from: https://tvst.arvojournals.org/article.aspx?articleid=2783469
13.   Martinez VV, Dutra BAL, Santhiago MR, Wilson SE. Effect of Topical Losartan in the Treatment of Established Corneal Fibrosis in Rabbits. Transl Vis Sci Technol [Internet]. 2024 Aug 12;13(8):22. Available from: https://tvst.arvojournals.org/article.aspx?articleid=2800678
14.   Martinez VV, Dutra BAL, Sampaio LP, Shiju TM, Santhiago MR, Wilson SE. Topical Losartan Inhibition of Myofibroblast Generation in Rabbit Corneas With Acute Incisions. Cornea. 2024;43(7):883–9.
15.   Uysal BS, Sarıkaya B, Dizakar SÖA, Kaplanoğlu GT, Gümüşderelioğlu M. Investigation of healing strategies in a rat corneal opacity model with polychromatic light and stem cells injection. J Photochem Photobiol B Biol [Internet]. 2024 Apr;253(December 2023):112874. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1011134424000344
16.   Zode GS, Sharma AB, Lin X, Searby CC, Bugge K, Kim GH, et al. Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma. Vol. 124, Journal of Clinical Investigation. 2014. p. 1956–65.
17.   Nayak A, Deveswaran R, Swati S, Srividhya L. Agreement of tonometer for measuring intraocular pressure in Wistar rats: a systematic review. Eur J Med Res [Internet]. 2024 Jun 16;29(1):332. Available from: https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-024-01927-z
18.   Martínez‐águila A, Martín‐gil A, Carpena‐torres C, Pastrana C, Carracedo G. Influence of circadian rhythm in the eye: Significance of melatonin in glaucoma. Vol. 11, Biomolecules. 2021. p. 1–25.
 
 
Eltiam
Volume 12, Issue 1 - Serial Number 23
November 2025
Pages 148-154

  • Receive Date 01 September 2025
  • Revise Date 18 September 2025
  • Accept Date 22 September 2025
  • Publish Date 22 November 2025