A Research Blog

Till now, transporters for DHA uptake in the eye have not been identified. Duke-NUS PhD student Bernice Wong has been able to show that the transporter Mfsd2a is found at the blood-retinal barrier (BRB) and is required for Docosahexaenoic acid (DHA) uptake in the eye – thereby proving Mfsd2a’s importance for normal eye development.Plastic sections of mice's eyes with blue staining to visualise the layers

DHA is highly enriched in the eye and is considered to be required for normal eye function. Photoreceptors are responsible for conferring vision, and its outer segments account for the highest body concentration of DHA per unit area. However, the eye does not synthesise DHA, and must import it from the blood. Like the blood-brain barrier (BBB), the eye too, has a BRB.

Bernice is the first author of this paper published in the Journal of Biological Chemistry (JBC), while its senior author is Professor David Silver, Director of Graduate Studies at Duke-NUS and the Deputy Director of the Duke-NUS Signature Research Programme in Cardiovascular and Metabolic Disorders.

Work previously published by Prof Silver demonstrated that Mfsd2a was the primary transporter for the uptake of DHA across the BBB in the chemical form of lysophosphatidylcholine (LPC). This was proven in mouse models and shown to be true in humans as well.

From left to right: Duke-NUS PhD student Bernice Wong, David SilverBernice and Prof Silver found Mfsd2a to be the transporter for DHA uptake in the eye, which is important for the development of photoreceptor membrane discs. They were able to do this by examining the eyes of mice with or without Mfsd2a, using multi-disciplinary approaches.

In this JBC study, Mfsd2a was found to be expressed at the BRB, primarily in the retinal pigment epithelium (RPE). Loss of LPC-DHA transport in Mfsd2a deficient eyes led to DHA deficiency, shortened and disorganised outer segments, and swollen RPE. Moreover, the Mfsd2a-deficient mice generated had intact BBBs and BRBs, which is contrary to a recent report by Dr Ayal Ben-Zvi and Prof Chenghua Gu from Harvard Medical School. The integrity of the BBB was confirmed using BBB leakiness experiments conducted by Jia Pei Chan, a Duke-NUS PhD student also supervised by Prof Silver.

The discovery of Mfsd2a at the RPE, means that the transporter function could be exploited for the delivery of small molecule therapeutics conjugated to LPC scaffolds for the treatment of eye diseases. Moving forward, Bernice and Prof Silver will be interested to understand the mechanism by which LPCs contribute to visual function.

For the study’s full text, click here.

This research is support by the National Research Foundation Singapore under its Cooperative Basic Research Grant  (NMRC/CBRG/0069/2014), the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2014-T2-2-018) and by the Singapore Ministry of Health’s National Medical Research Council under its Centre Grant (NMRC/CG/SERI/2013).

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