Abstract
Purpose :
Photoreceptors are metabolically demanding first-order neurons. The deep capillary plexus sustains synaptic interactions between photoreceptors and horizontal and bipolar cells. Mitochondria produce energy in the form of ATP to support the activities of retinal cells via uptake of oxygen from the retinal vasculature. Prior studies showed mitochondrial migration towards blood sources during retina development (PMID 18048005). The purpose of this study was to determine the distribution of mitochondria in cells participating in the neurovascular unit of the outer plexiform layer in human retina, of relevance to retinal vascular disease.
Methods :
Parafoveal retina of a 21-year-old male organ donor was dissected and placed into oxygenated Ames medium and fixed in 4% glutaraldehyde. Vertical sections were acquired using serial block-face electron microscopy at a voxel size of 5×5×50 nm3 and registered using TrakEM2 (NIH). In the outer plexiform layer surrounding the deep vascular plexus, cone and bipolar cells and within them, individual mitochondria was reconstructed in 3-dimensions using supervised deep-learning enabled segmentation (ORS Dragonfly, Canada).
Results :
Complete reconstructions of processes in and near the deep capillary plexus revealed numerous cone bipolar dendrites encircling a vessel. The capillary was also ensheathed by Müller cells without identifiable mitochondria. Mitochondria within bipolar neurons surrounding the capillary exhibited a long and slender morphology extending through the dendritic course encircling the capillary. Reconstructions of outer plexiform layer revealed multiple bipolar cells with mitochondria-filled blind processes lacking synaptic terminals and descending into the Henle fiber layer. Reconstructions of cone pedicles revealed clusters of ovoid mitochondria. Mitochondria counts in cone pedicles adjacent to the capillary were higher (mean 54.4 ± 9.7, range 66-44, n=6) than in pedicles distant from the capillary (35.2 ± 7.75, 43-27; n=6).
Conclusions :
Initial findings of this ongoing study suggest cellular-level variations in mitochondrial morphology and distribution in cone pedicles and bipolar dendrites in relation to vascular oxygen sources. Findings are relevant to the cellular basis of underlying mechanisms involved in compromised oxygen supply to the outer plexiform layer in type 3 neovascularization and paracentral acute middle maculopathy.
This is a 2021 ARVO Annual Meeting abstract.