NEUROPROTECTIVE ROLE OF VITAMIN D3 ON GANGLION CELL-INNER PLEXIFORM LAYER THICKNESS IN NMDA-INDUCED RETINAL EXCITOTOXICITY MODEL OF GLAUCOMA (Experimental Study on Wistar Rats Glaucoma Model with N-Methyl-D-Aspartate induction)
Abstract
Introduction & Objectives
Retinal ganglion cell (RGC) damage can affect the thinning of the GCC layers, which is the nerve
fiber layer, the ganglion cell layer and the inner plexiform layer. The loss of RGC and inner plexiform
layer (IPL) is strongly correlated with the loss of visual field defect. RGC and inner plexiform layer
are potential targets to evaluate the progression of glaucoma. Glaucoma treatment not only focus on
reducing IOP. Decreasing IOP according to the target pressure often can’t stop the process of RGC
damage and make it permanently and irreversible. Vitamin D3 is known as neuroprotector which has
the ability to protect RGC and prevent layer thinning of GC-IPL in retina. The aim of this study is to
determine the effect of oral Vitamin D3 on the GC- IPL layer thickness in retinal of Wistar rats with
NMDA-induced glaucoma model.
Methods
Glaucoma Wistar rats were divided into 2 groups. The treatment group was given oral Vitamin D3 at
a dose of 500 IU/kgBW/day for 10 weeks. GC-IPL layer thickness in retinal was examined by
Hematoxylin Eosin staining. Data were collected and processed then used with Independent T Test.
(significant p<0.05)
Results
The mean GC-IPL layer Thickness in the treatment group was 77,59 ± 15,15 ?m and 35,32 ± 4,04
?m in the control group. There was a significant different between two group ( p = <0,001 )
Conclusion
Vitamin D3 has a neuroprotective effect on ganglion cell-inner plexiform layer Wistar rats in NMDAinduced
excitotoxicity model of glaucoma
Full text article
References
InfoDatin, Pusat Data dan Informasi Kementerian Kesehatan RI. Situasi Gangguan Penglihatan dan Kebutaan. Oktober 2014 : 2-3.
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):2081–90.
Rolle T, Ponzetto A, Malinverni L. The Role of Neuroinflammation in Glaucoma: An Update on Molecular Mechanisms and New Therapeutic Options. Front Neurol. 2021;11:1–9.
Zivkovic M, Dayanir V, Zlatanovic M, et al. Ganglion Cell-Inner Plexiform Layer Thickness in Different Glaucoma Stages Measured by Optical Coherence Tomography. Ophthalmic Res. 2018;59(3):148-154. doi:10.1159/000478052 5. Jiang S, Kametani M, Chen DF. Adaptive Immunity: New Aspects of Pathogenesis Underlying Neurodegeneration in Glaucoma and Optic Neuropathy. Front Immunol. 2020;11:1–5.
Christensen I, Lu B, Yang N, Huang K, Wang P, Tian N. The Susceptibility of Retinal Ganglion Cells to Glutamatergic Excitotoxicity Is Type-Specific. Front Neurosci. 2019;13(March):1–14.
Gao L, Zheng QJ, Ai LQY, Chen KJ, Zhou YG, Ye J, et al. Exploration of the glutamate-mediated retinal excitotoxic damage: A rat model of retinal neurodegeneration. Int J Ophthalmol. 2018;11(11):1746–54.
Kuehn S, Rodust C, Stute G, Grotegut P, Meißner W, Reinehr S, et al. Concentration-Dependent Inner Retina Layer Damage and Optic Nerve Degeneration in a NMDA Model. J Mol Neurosci. 2017;63:283–99.
Lambuk L, Jafri AJA, Iezhitsa I, et al. Dosedependent effects of NMDA on retinal and optic nerve morphology in rats. Int J Ophthalmol 2019;12(5):746- 753.
Cheng WS, Lin IH, Feng KM, Chang ZY, Huang YC, Lu DW. Neuroprotective Effects of Exogenous Erythropoietin in Wistar Rats by Downregulating Apoptotic Factors to Attenuate N-Methyl-DAspartate-Mediated Retinal Ganglion Cells Death. PLoS One [Internet]. 2020;15(4):1–2 DOI: http://dx.doi.org/10.1371/journal.pone.022 3208
Vishwaraj CR, Kavitha S. Neuroprotection in glaucoma. IndianJOphthalmol. 2022;70:380-5.
Boia R, Ruzafa N, Aires ID, Pereiro X, Ambrósio AF, Vecino E, et al. Neuroprotective strategies for retinal ganglion cell degeneration: Current status and challenges ahead. Int J Mol Sci. 2020;21(7):1–39.
Chan H, Zhang X, Ling X, Bui CH, Wang Y, Ip P, et al. Vitamin D and Ocular Diseases : A Systematic Review. 2022;158.
Alsalem JA, Rauz S, Wallace GR. Vitamin D: Presence and Function in the Eye. [Internet]. Fourth Edition. Vol. 2, Vitamin D: Fourth Edition. Elsevier; 2017. 1131–1146 p. DOI: http://dx.doi.org/10.1016/B978-012-809963- 6.00114-0
Kalueff A V., Eremin KO, Tuohimaa P. Mini-review: Mechanisms of neuroprotective action of Vitamin D3. Biokhimiya. 2004;69(7):907–11.
Fernandez-Robredo P, González-Zamora J, Recalde S, Bilbao-Malavé V, Bezunartea J, Hernandez M, et al. Vitamin D Protects Against Oxidative Stress and Inflammation In Human Retinal Cells. Antioxidants. 2020;9(9):1–18.
Kim HT, Kim JM, Kim JH, et al. The Relationship between Vitamin D and Glaucoma: A Kangbuk Samsung Health Study. Korean J Ophthalmol 2016;30(6):426-433
Alrefaie Z, Alhayani A. Vitamin D3 improves decline in cognitive function and cholinergic transmission in prefrontal cortex of streptozotocin-induced diabetic rats. Behav Brain Res [Internet]. 2015;287:156–62. Available from: http://dx.doi.org/10.1016/j.bbr.2015.03.05 0
Lu L, Lu Q, Chen W, Li J, Li C, Zheng Z. Vitamin D3 protects against diabetic retinopathy by inhibiting high-glucoseinduced activation of the ROS/TXNIP/NLRP3 inflammasome pathway. J Diabetes Res. 2018
Wimalawansa SJ. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology (Basel). 2019;8(2):30.
Ali A, Shah SA, Zaman N, Uddin MN, Khan W, Ali A, Riaz M, Kamil A. Vitamin D exerts neuroprotection via SIRT1/nrf-2/ NF-kB signaling pathways against D-galactoseinduced memory impairment in adult rats. Neurochem Int. 2021;142:104893.
AlJohri R, AlOkail M, Haq SH. Neuroprotective role of Vitamin D in primary neuronal cortical culture. eNeurologicalSci. 2018;14:43-48 23. Šimoli?nas E, Rink?nait? I, Bukelskien? Ž, Bukelskien? V. Bioavailability of different Vitamin D oral supplements in laboratory animal model. Med. 2019;55(6):1–8.
Ren Z, Li W, Zhao Q, Ma L, Zhu J. The impact of 1,25-dihydroxy Vitamin D3 on the expressions of vascular endothelial growth factor and transforming growth factor-?1 in the retinas of rats with diabetes. Diabetes Res Clin Pract [Internet]. 2012;98(3):474–80. Available from: http://dx.doi.org/10.1016/j.diabres.2012.0 9.028
Morello M, Landel V, Lacassagne E, Baranger K, Annweiler C, Féron F, et al. Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer’s Disease. Mol Neurobiol. 2018;55(8):646379.
AlJohri R, AlOkail M, Haq SH. Neuroprotective role of Vitamin D in primary neuronal cortical culture. eNeurologicalSci [Internet]. 2019;14(November 2017):43–8. Available from: https://doi.org/10.1016/j.ensci.2018.12.00 4
Nakazawa T, Shimura M, Endo S, Takahashi H, Mori N, Tamai M. N-Methyl- D-Aspartic Acid Suppresses Akt Activity Through Protein Phosphatase In Retinal Ganglion Cells. Mol Vis. 2005;11(12):1173–82.
Thomas CN, Berry M, Logan A, Blanch RJ, Ahmed Z. Caspases in retinal ganglion cell death and axon regeneration. Cell Death Discov. 2017;3(1):1–13.
Authors
Copyright (c) 2023 Ezra Margareth, Trilaksana Nugroho, Andhika Guna Dharma, Fifin L Rahmi, Maharani, Hermawan Istiadi
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