Abstract
Purpose :
The omega-3 fatty acid docosahexaenoic acid (DHA) is an essential component of neural membranes and has an anti-inflammatory and neuroprotective effect on the retina. DHA is being widely administered to patients with neurodegenerative diseases, as diminished levels of this fatty acid were found in the central nervous system of these patients and of animal models with neural diseases. Nevertheless, the transport mechanism of DHA remains unclear in the retina. MFSD2a was described as the putative transporter of DHA in the blood-retina barrier, but it is unknown if this protein is expressed in the neurons. We assessed to describe if this transporter is expressed in the neural retina using immunofluorescence.
Methods :
We performed immunohistochemistry with anti-MFSD2a and specific markers of retinal populations in cryostat sections of the human retina. We used the transcriptional factors Chx10 for the identification of pan-bipolar cells, Pax6 for amacrine cells, and Brn3a for ganglion cells. For the identification of horizontal cells, we used parvalbumin. We identified the Müller cells and the retinal pigmented epithelium (RPE) with anti-CRALBP, and the cones with anti-cone arrestin. Additionally, we used LaminB2 to detect the nuclear membrane and KDEL and SERCA2 for the immunodetection of the endoplasmic reticulum.
Results :
MFSD2a was extensively expressed in the neural retina. We have found that MFSD2a is expressed in the inner segments of photoreceptor cells, as well as in the outer nuclear layer, where somas of photoreceptor cells are localized. We also detected immunostaining in the inner nuclear layer, as well as in the ganglion cell layer. In the double immunostaining with the transcriptional factors Chx10, Pax6, and Brn3a we have found that all bipolar, amacrine, and ganglion cells expressed the DHA transporter. Horizontal cells also expressed MFSD2a in their nucleus. Müller cells showed anti-MFSD2a immunoreaction in the external limiting membrane. However, the RPE did not show immunolabeling with anti-MFSD2a. We have found MFSD2a immunolabelling in the endothelial cells of the blood vessels of the human retina.
Conclusions :
MFSD2a is expressed by endothelial cells of the human retina, but also by the neural cells. Photoreceptor cells, Müller cells, and all populations of bipolar, amacrine, horizontal, and ganglion cells expressed MFSD2a in their cytosol and in their nuclear membrane.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.