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The Role of Vitamin D3 in Preventing Ethambutol-induced Toxic Optic Neuropathy on Wistar Rat Model: A Pilot Study

1Doctoral Study Program of Medical and Health Science, Universitas Diponegoro, Indonesia

2Department of Ophthalmology, Faculty of Medicine, Universitas Diponegoro, Indonesia

3Department of Neurology, Faculty of Medicine, Universitas Diponegoro, Indonesia

Received: 4 Nov 2025; Revised: 20 Mar 2026; Accepted: 14 Apr 2026; Available online: 29 Aug 2026; Published: 31 Aug 2026.
Open Access Copyright (c) 2026 Journal of Biomedicine and Translational Research
Creative Commons License This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

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Abstract

Background: Ethambutol toxic optic neuropathy (ETON) is one of the side effects of ethambutol (EMB) therapy in tuberculosis (TB) patients which can cause visual impairment. Prevention of this neurotoxicity is effective strategy to address this condition. Vitamin D3 has the potential to prevent ETON since vitamin D3 is a neuroprotective agent.

Objective: To observe the effect of vitamin D3 in ETON wistar rat model through its effect on the excitotoxicity pathway.

Methods: This study used a true experimental, post-test-only randomized controlled design. Fourteen Wistar rats were randomly divided into two groups. All rats received EMB at a dose of 32 mg per 200 g body weight per day for 30 days. The treatment group also received oral vitamin D3 at 72 IU per 200 g body weight per day. NMDA receptor expression was examined using immunohistochemical (IHC) staining, and retinal ganglion cell (RGC) density was analyzed using Hematoxylin-Eosin (HE) staining. Differences in NMDA receptor expression were tested using the Mann–Whitney test, while RGC density was analyzed with an Independent T-test followed by Spearman’s correlation test.

Results: The expression of NMDA receptors in the treatment group given vitamin D3 was lower than the control (62.00 ± 16.43 and 70.00 ± 7.07, respectively) with no statistically significant result (p=0.502). Retinal ganglion cell density in the treatment group was higher and statistically significant when compared with the control group (11.36 ± 0.51 and 9.60 ± 1.14, p=0.014). The results of the Spearman's correlation test between NMDA receptor expression and RGC density were found to be p=0.380.

Conclusion: Oral vitamin D3 has an effect to increase RGCs density in rats given ethambutol.

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Keywords: Vitamin D3; cholecalciferol; ethambutol; toxic optic neuropathy; NMDA receptor; retinal ganglion cells

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Section: Original Research Articles
Language : EN
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