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The effect of palm oil-derived tocotrienol-rich fraction in preserving normal retinal vascular diameter in streptozotocin-induced diabetic rats

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Abstract

Purpose

Angiogenesis in diabetic retinopathy (DR) is associated with increased retinal expression of angiopoietin-2 (Ang-2) and protein kinase C (PKC). Tocotrienol-rich fraction (TRF) has been shown to reduce the expression vascular endothelial growth factor (VEGF) in several experimental models. However, its effect against other angiogenic markers such as Ang-2 and PKC in rat model of diabetes remains unknown. Therefore, we investigated the effect of TRF on the retinal vascular changes and Ang-2 and PKC expressions in rats with streptozotocin (STZ)-induced DR.

Methods

Sprague–Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions.

Results

Retinal venous and arterial diameters were significantly greater in DV compared to DT at week 12 post-STZ injection (p < 0.001 and < 0.05, respectively). The vessel diameter measurements in DT were comparable to N and this effect of TRF was associated with significantly lower Ang-2 and PKC gene and protein expressions compared to DV.

Conclusion

Oral TRF reduces the expression of retinal angiogenic markers and preserves the retinal vascular diameter of rats with STZ-induced DR.

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Data transparency

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the administrative and facility support by Research Management Centre, Institute of Medical Molecular Biotechnology (IMMB) and Laboratory Animal Care Unit (LACU), Universiti Teknologi MARA, Malaysia.

Funding

This work was supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education (MoHE) (600-IRMI/FRGS 5/3 (101/2019)) and Malaysian Society of Ophthalmology small research grant.

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Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Medicine, University Malaya Eye Research Centre, University of Malaya, Kuala Lumpur, Malaysia

    Nurliyana Ain Abdul Ghani & Norlina Ramli

  2. Department of Ophthalmology, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia

    Nurliyana Ain Abdul Ghani

  3. Centre for Neuroscience Research, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia

    Nurul Alimah Abdul Nasir, Lidawani Lambuk & Muhammad Zulfiqah Sadikan

  4. Department of Pharmacology, Faculty of Medicine, Manipal University College Malaysia (MUCM), Bukit Baru, 75150, Melaka, Malaysia

    Muhammad Zulfiqah Sadikan

  5. School of Medicine, International Medical University, Kuala Lumpur, Malaysia

    Renu Agarwal

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Contributions

NAAG, NAAN, and RA conceived the research and designed the experiment. NAAG, MZS, and LL performed experiments and analysis. NAAN, RA, and NR participated in the interpretation of the data. NAAG drafted the manuscript. NAAN, RA, and NR supervised and revised the manuscript. All authors contributed to the manuscript and approved the submitted version.

Corresponding author

Correspondence to Nurul Alimah Abdul Nasir.

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Ethical approval

This study was approved by the local institutional animal ethics committee (Universiti Teknologi MARA Committee of Animal Research and Ethics) under approval number 3/2019/(286/2019).

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors have jointly decided to designate NAAN to be responsible for decision-making regarding the presence of authors and the order of their presence in the manuscript. NAAN has also been selected by all authors to be responsible for all future communication with the journal regarding this manuscript.

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Abdul Ghani, N.A., Abdul Nasir, N.A., Lambuk, L. et al. The effect of palm oil-derived tocotrienol-rich fraction in preserving normal retinal vascular diameter in streptozotocin-induced diabetic rats. Graefes Arch Clin Exp Ophthalmol 261, 1587–1596 (2023). https://doi.org/10.1007/s00417-022-05965-3

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