A study on ground squirrels shows, not only do mitochondria produce bioenergy in the cone-shaped photoreceptors in the retina of the eye, they also act as micro-lenses that redirect light to the tapering outer reaches of these cells where light is converted into electrical signals.

The finding, published on March 2, 2022, in the journal Science Advances (“Mitochondria in cone photoreceptors act as microlenses to enhance photon delivery and confer directional sensitivity to light“) by scientists at the National Eye Institute (NEI) provides a clearer picture of the evolution and physiology of vision and  the retina’s illusive optical properties. Insights from the study could also help in the early detection of eye diseases.

Mitochondria in cone photoreceptors serve a dual purpose. They generate energy and act as microlenses. Mitochondria concentrates light as it moves from the cone’s inner to outer segment where the light’s physical energy is translated into cellular signals (NEI)

The study’s senior author, Wei Li, PhD, principal investigator at the NEI Retinal Neurophysiology Section, said, “We were surprised by this fascinating phenomenon that mitochondria appear to have a dual purpose: their well-established metabolic role producing energy, as well as this optical effect.”

Once light reaches the retina, it must pass through several neural layers to reach the outer segment of photoreceptors, where light’s physical energy is converted into neural signals through a process called phototransduction. Between the inner and outer segment of the cone photoreceptors lie a dense bundle of mitochondria that light must traverse to be transduced. Although it might appear these mitochondria pose an obstacle to the process of vision by either scattering or absorbing light, the current study shows they serve a unique function to facilitate vision.

Li’s team investigated the role of mitochondria in cone photoreceptors in the 13-lined ground squirrel. The 13-lined ground squirrel’s retina comprises mostly cones, which detect color, unlike rod-shaped photoreceptors that help in seeing in low light.

Using a modified confocal microscope to observe the optical properties of living cone mitochondria exposed to light, the researchers observed that instead of scattering light, the tightly packed mitochondria concentrated light along a pencil-like trajectory onto the light-sensitive outer segment. High-resolution mitochondrial reconstructions corroborated the live-imaging findings. In addition, the authors show remodeling mitochondrial architecture affects this concentration of light.

Electromagnetic simulations of light concentration by cone mitochondria of ground squirrels (NEI).

“The lens-like function of mitochondria also may explain the phenomenon known as the Stiles Crawford effect,” said John Ball, PhD, a staff scientist in the Retinal Neurophysiology Section and first author of the paper. The Stiles Crawford effect that improves visual resolution describes a basic phenomenon where light entering the eye through the periphery of the pupil does not appear as bright as light passing through its center.

Li’s team found that the lens-like effect of mitochondria followed a similar directional light intensity profile as the Stiles Crawford effect. Depending on the location of the light source, mitochondria in cones focused light into the outer segment of the cell mirroring the Stiles Crawford effect.

Linking mitochondria’s optical role to the Stiles-Crawford effect suggests. the established effect may be used for the non-invasive detection of retinal diseases, many of which are believed to involve mitochondrial dysfunction. For example, patients with retinitis pigmentosa have been reported to have abnormal Stiles-Crawford effect even though their visual acuity is unaffected.

The study also sheds new light on how our eyes may have evolved. Within the photoreceptors of birds and reptiles, tiny oil droplets at the junction of the inner and outer segments that may play an optical role are reminiscent of the lipid-rich mitochondria of cones in the current study on ground squirrels. Moreover, the mitochondrial “microlens” in mammalian cone photoreceptors is functionally like the biological effect achieved by the compound eye in insects.

Li said, “This insight conceptually bridges compound eyes in arthropods with the camera eyes of vertebrates, two independently evolved image-forming systems, demonstrating the power of convergent evolution.”

In future studies, the team intends to explore structural and functional changes in cone mitochondria and how these affect the optics of the eye.