Vision scientists uncover a new angle on the path of light through photoreceptors

Press release

Wednesday, March 2, 2022

An NIH study in ground squirrels suggests a dual function for mitochondria in photoreceptor cells.

Researchers from the National Eye Institute (NEI) have found that energy-producing organelles in the eye’s photoreceptor cells, called mitochondria, function like microlenses that help channel light to the outer segments of these cells where it is converted into nerve signals. The finding in ground squirrels provides a more accurate picture of the optical properties of the retina and could help detect eye disease earlier. The results, published today in Science Advances, also shed light on the evolution of vision. NEI is part of the National Institutes of Health.

“We were surprised by this fascinating phenomenon that mitochondria appear to serve a dual purpose: their well-established metabolic role in energy production, as well as this optical effect,” said study lead researcher Wei Li. , Ph.D./BM, who directs the NEI’s Retinal Neurophysiology Section.

The findings also address a long-standing mystery about the mammalian retina. Despite evolutionary pressure for light to be translated into signals and travel instantaneously from the retina to the brain, the journey is hardly direct. Once light reaches the retina, it must pass through several neural layers before reaching the outer segment of photoreceptors, where phototransduction (the conversion of physical light energy into cellular signals) occurs. Photoreceptors are long tubular structures divided into inner and outer segments. The final hurdle a photon must cross before passing from the inner segment to the outer segment is an exceptionally dense bundle of mitochondria.

These bundles of mitochondria appear to act against the vision process either by scattering light or by absorbing it. So Li’s team set out to investigate their goal by studying the conical photoreceptors of the 13-lined ground squirrel.

Unlike other animal models used for vision research, the retina of the 13-line ground squirrel primarily comprises cones, which see color, as opposed to rods, which provide night vision. Li’s team is studying the 13-lined ground squirrel to better understand the causes of human eye diseases that primarily affect cone photoreceptors.

The researchers used a modified confocal microscope to observe the optical properties of live cone mitochondria exposed to light. Far from scattering light, the tightly packed mitochondria focused light along a thin, pencil-shaped path on the outer segment. Computer modeling using high-resolution mitochondrial reconstructions corroborated the results from live imaging.

“Mitochondria’s lensing function may also explain the phenomenon known as the Stiles Crawford effect,” said the paper’s first author, John Ball, Ph.D., a researcher in the Section of Retinal Neurophysiology.

Scientists measuring retinal responses to light have long observed that when light enters the eye near the center of the pupil, it appears brighter compared to light of equal intensity entering the eye near the edge. of the pupil.

In this study, Li found that mitochondria lensing followed a similar directional light intensity profile. That is, depending on the location of the light source, mitochondria focused light into the outer segment of the cell along trajectories mirroring those observed from the Stiles-Crawford effect.

Linking the lens function of mitochondria to the Stiles-Crawford effect has potential clinical implications. The long observed effect can now be used as a basis for non-invasively detecting retinal diseases, many of which are thought to involve mitochondrial dysfunction at their origin. For example, patients with retinitis pigmentosa have been reported to exhibit an abnormal Stiles-Crawford effect even when they had good visual acuity. Further research is needed to explore structural and functional changes in cone mitochondria and their manifestations in detectable optical features.

Finally, the results provide new insights into how our eyes may have evolved.

Like the mitochondria in Li’s study, in the photoreceptors of birds and reptiles, tiny oil droplets are located in the part of the inner segment closest to the outer segment, and they are thought to play an optical role . Additionally, the mitochondrial “microlens” of mammalian cone photoreceptors confers functionality reminiscent of that achieved by the compound eye of arthropods such as flies and bumblebees.

“This idea conceptually links arthropod compound eyes to vertebrate camera eyes, two independently evolved imaging systems, demonstrating the power of convergent evolution,” Li said.

The study was funded by the NEI Intramural Research Program.

NEI leads federal government research on the visual system and eye disease. NEI supports basic and clinical science programs to develop sight-saving treatments and address the special needs of people with vision loss. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH):The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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Reference:

Ball JM, Chen S, Li W. “Mitochondria in conical photoreceptors act as microlenses to enhance photon delivery and confer directional light sensitivity”, published March 2, 2022 in Science Advances. DOI: https://doi.org/10.1126/sciadv.abn2070

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