Integrative and Comparative Biology
Integrative and Comparative Biology, volume 56, number 5, pp. 758–763
doi:10.1093/icb/icw106
Society for Integrative and Comparative Biology
SYMPOSIUM INTRODUCTION
Extraocular, Non-Visual, and Simple Photoreceptors: An
Introduction to the Symposium
Thomas W. Cronin1,* and Sönke Johnsen†
*Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21043, USA; †Department
of Biology, Duke University, Durham, NC 27708, USA
From the symposium ‘‘Extraocular, Nonvisual, and Simple Photoreceptors’’ presented at the annual meeting of the
Society for Integrative and Comparative Biology, January 3–7, 2016 at Portland, Oregon.
1
E-mail: [email protected]
Synopsis It has been recognized for decades that animals sense light using photoreceptors besides those that are devoted
strictly to vision. However, the nature of these receptors, their molecular components, their physiological responses, and
their biological functions are often obscure. Only recently have researchers begun to learn how critical these non-visual or
very simple visual responses are to organismal function. New approaches, including high-throughput molecular genetic
techniques, have led to a revolution in our understanding of the evolution, anatomical distribution, physiology, and—in
some cases—function of non-visual photoreception in diverse organisms. In the following papers, we bring together
specialists from throughout the field to review the current state of knowledge regarding extraocular, non-visual, and
simple photoreceptors in a large diversity of organisms ranging from protists through vertebrates and invertebrates.
Introduction
As visual creatures, we humans are very aware of the
critical significance of the information we gather
using our image-forming eyes and image-analyzing
nervous systems. Most of this visual input is available
to our conscious minds, and it provides us with a
rich and vital sensory experience. What is not so obvious is that there is a parallel stream of information
that arrives from light stimuli that runs below the
level of consciousness. While not accessible to our
consciousness, this flow of photosensitivity is nevertheless is critical to our function. It has been recognized for decades that many organisms sense light
using photoreceptors besides those that are used for
vision, although the nature of these receptors, their
molecular components, their physiological responses,
and their biological function are often obscure.
Historically, these types of receptors have been described primarily among invertebrates, although they
are widespread among fish, amphibians, reptiles, and
birds as well. Their presence in mammals was completely unsuspected until the end of the 20th century.
Somewhat surprisingly, work in extraocular and
non-visual photoreception has not been synthesized
for some time. Hundreds of papers have been published in recent years on non-visual photoreception in
various organisms (including mammals), but the last
review of which we are aware was that of Yoshida,
published nearly four decades ago (Yoshida 1979),
and this concerned only invertebrates. New
approaches, including high-throughput molecular genetic techniques, have led to a revolution in our understanding of the evolution and function of nonvisual photoreception in diverse animals, particularly
in the arthropods, molluscs, and vertebrates. Thus,
the fundamental roles and mechanisms of nonvisual processes are finally beginning to be revealed.
In view of all this, we felt that the time had
come to organize a symposium that covers the
full range of photosensitive organisms from
single-celled protists to physiologically complex
protostome and deuterostome animals. Our hope
was that such an integrative approach would be
useful both to the participants in their ongoing
research and to others throughout the biological
sciences who wish to learn more about the diversity of photoreceptive systems besides the ones devoted solely to vision.
Advanced Access publication August 4, 2016
ß The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.
All rights reserved. For permissions please email: [email protected].
Photoreceptors
Terminology
Extraocular photoreceptor
An extraocular photoreceptor is a cell or relatively
simple light-sensitive structure that is found outside
of an eye. Here, an eye is defined as an organ with
some sort of optical system and a spatially extended
retina (we will return to this later on in the definition of a ‘‘simple photoreceptor’’). Eyes are visual
organs; that is, they confer a sense of space and
motion to the central nervous system based on electromagnetic input. Until recently, all known photoreceptors that do not contribute directly to vision
were found outside of eyes (e.g., Yoshida 1979).
However, the discovery of intrinsically photosensitive
retinal ganglion cells (ipRGCs) in vertebrates by
Provencio et al. (1998) demolished this paradigm.
These particular ganglion cells are largely involved
in processes that lie below the level of vision, such
as circadian entrainment, sleep-wake cycles, general
alertness, or the pupillary reflex (Kingston and
Cronin 2016; Sonoda and Schmidt 2016). Thus,
they handle functions that are usually the provenance
of extraocular photoreceptors.
Non-visual photoreceptor
This term refers to light-sensitive cells that do not
contribute to a perception of spatial location or
motion. All extraocular photoreceptors are by definition non-visual, but this term has become useful
because some photoreceptors in eyes (e.g., many
ipRGCs) evidently do not communicate with visual
centers in the nervous system (but see Sonoda and
Schmidt 2016). In some animals, parts of the eye
besides the retina are photosensitive, including the
iris of some vertebrates (e.g., frogs: Barr and
Alpern 1963; Kargacin and Detwiler 1985). Not
being extraocular, these sorts of light detectors are
now called non-visual photoreceptors, but they function using mechanisms similar or identical to those
of classical extraocular photoreceptors.
Simple photoreceptors
This term is not formal, but it became necessary in
the context of this symposium because there are
light-sensitive systems in protists and animals that
probably contribute to, at best, rudimentary vision
and probably have functions typical of extraocular
photoreceptors as well (although this has not been
documented, to our knowledge). In some cases, these
sorts of photoreceptors are themselves single-celled
organisms (e.g., Colley and Nilsson 2016), whereas
in others, they are grouped into something like a
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typical eye but contribute to shadow responses or
other behaviors that are not concerned with the location of the stimulus (e.g., Bok et al. 2016). The
shell eyes of chitons and the mantle eyes of scallops
(Speiser 2016; Speiser et al. 2011) lie in the hazy
interval between non-visual and visual structures,
but their multiplicity, lack of overall organization
as an ensemble, temporary existence, and contribution to simple, non-oriented behaviors led us to include them in the symposium.
The photopigments of extraocular, nonvisual, and simple photoreceptors
The most common and widespread light-sensitive
molecules in animals are visual pigments based on
an opsin protein joined to a chromophore, usually
retinaldehyde, also known as retinal1 (Porter 2016;
Porter et al. 2012). Opsins are G-protein coupled
receptors (GPCRs) that, when activated by the absorption of a photon by the chromophore, in turn
activate a GTP-binding protein, or G-protein, which
then goes on to influence biochemical events that
ultimately lead to the opening or closing of ion
channels in the plasma membrane. G-proteins themselves are diverse, and different members of the
family influence different intracellular processes.
Because the particular opsin involved in light detection in a given cell will selectively bind a single type
of G-protein, the type of opsin employed will largely
determine the type of cellular response that occurs
upon light stimulation. This complex regulatory process, no doubt, partly explains the confusing profusion of novel opsins that occur in non-visual
photoreceptors (Battelle 2016; Porter 2016) and for
the appearance of invertebrate-like opsins in vertebrate retinas (Sonoda and Schmidt 2016).
The various types of photoreceptors discussed in
this symposium frequently employ unusual opsins,
activating varying G-protein-mediated cascades,
switching on different cellular responses, and ultimately producing different organismal events. This
functional flexibility probably is an important
aspect of non-visual signaling. On the other hand,
some non-visual photoreceptors use opsins that are
identical to those of retinal photoreceptors devoted
to imaging vision in the same organism and that
apparently employ identical mechanisms of phototransduction as well (Kingston and Cronin 2016).
As a consequence of this, the polarity of the evolutionary connection between retinal opsins involved
in vision and extraocular (or non-visual) opsins
760
devoted to other physiological or sensory events is
often obscure.
Although opsins are the only receptor proteins
known to be involved in vision, other light-sensitive
pigments can contribute to non-visual photoreception. In the organisms considered in this symposium,
by far the most common of these pigments is cryptochrome. The evolution and function of the cryptochromes in animals are not well understood, and the
associated cellular pathways used in animals are also
obscure (Partch and Sancar 2005). Light-sensing
cryptochromes are thought to mediate processes as
diverse as phototaxis in sponge larvae (Rivera et al.
2012), magnetoreception in birds (Mouritsen et al.
2004) and insects (Gegear et al. 2010), and circadian
rhythms in Drosophila (Stanewsky et al. 1998). In the
squid Euprymna scolopes, endosymbiotic, bioluminescent bacteria in the light organ influence expression
of cryptochrome in the host animal, apparently
through mechanisms that themselves are regulated
by the light they produce (Heath-Heckman et al.
2013, 2016). While it is obvious that cryptochromes
are involved in many processes requiring light detection, the ‘‘crypto’’ aspect of their name continues to
reflect our ignorance about them.
Light sensing is probably handled through other
photosystems besides the opsins and cryptochromes,
although at present there is only one example. In the
nematode Caenorhabditis elegans and in larval
Drosophila, there is a gustatory receptor homolog
that is thought to modulate phototaxis (Liu et al.
2010; Xiang et al. 2010). As detecting light seems
to be such a critical organismal function, any cellular
component that can act as a photopigment and can
couple to a cellular signaling system is available for
co-opting into a non-visual photosensing system.
So far, we have primarily discussed animal photoreception. Yet plants respond to light, and some
plants (as well as multicellular protists) ‘‘behave’’
in response to light. The eukaryotic, single-celled
protists covered in this symposium (Colley and
Nilsson 2016) are essentially ‘‘motile photoreceptors’’—organisms that both sense light and generate
movement responses to it. Their light sensors also
involve molecules similar to opsins, binding a retinoid chromophore and having seven trans-membrane helices, but that are not true GPCRs. Instead,
these molecules usually act as selective ion channels
or pumps that are gated by light reception. The photoreceptive molecules in eukaryotes are called channelrhodopsins, and are included with bacterial
rhodopsins and halorhodopsins in the ‘‘Type I
Opsins’’ (animal opsins are often called ‘‘Type II
Opsins’’). See the papers that follow by Porter
T. W. Cronin and S. Johnsen
Fig. 1 A general scheme of the evolution of eyes, modified from
Nilsson (2009). Complex imaging eyes appear at the upper right.
The types of photoreceptors and simple pre-visual organs considered in this symposium occur mostly at the lower three levels
to the left, but note that molluscan simple eyes often have imaging optics. The trajectory of evolution of extraocular, nonvisual, and simple photoreceptors does not necessarily flow from
left to right.
(2016) and by Colley and Nilsson (2016) for more
about the diversity of photopigments in living
photoreceptors.
Evolution of extraocular, non-visual, and
simple photoreceptors
A common assumption is that the sorts of photoreceptors considered here appeared before the appearance of complex visual organs. To illustrate this, we
have borrowed the conceptual diagram created by
Nilsson (2009) to suggest the evolution of complex
eyes (Fig. 1). Nilsson (2009) conceived this scheme
to show how eye design reflects the required visual
task, with ever-more-complex eye types providing
higher and higher levels of acuity and temporal resolution. A species with complex behavior and the
need to make rapid, oriented responses requires an
acute eye that provides the necessary input, as with
the designs lying at the top right corner of the figure.
However, non-visual tasks are best served by small
and simple eyes, ones that are as energy-efficient as
possible. In Nilsson’s scheme, these are the types
found in the lower left regions of the figure, needing
only decent systems for maintaining photopigment
(i.e., chromophore recycling) and for converting
photon absorption into a cellular signal (phototransduction). As task complexity increases, other features
Photoreceptors
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Fig. 2 Examples of the types of photoreceptors and simple eyes considered in this symposium. (A) Intrinsically photosensitive retinal
ganglion cell of a mouse (green; courtesy Maureen E. Stabio). (B) Ventral photoreceptor of the horseshoe crab Limulus polyphemus. The
green label shows the presence of peropsin in surrounding glia; red is the rhabdomere (courtesy of Barbara Battelle). (C) Simple mirror
eyes (blue circles) of the bay scallop Argopecten irradians. (D) Chromatophore of the squid Doryteuthis pealeii, colabeled with antibodies
against squid opsin (green) and retinochrome (red) (courtesy of Alexandra Kingston). (E) Aboral surface of the purple sea urchin
Strongylocentrotus purpuratus; opsin protein exists in the tube feet (tiny reddish circles) and pedicellariae. (F) Intracellular ‘‘eye’’ of a
warnowiid dinoflagellate (tentatively identified as Proterythropsis sp.; after Hoppenrath et al. 2009). (G) Simple shell-embedded eyes
(dark, shiny structures) of the chiton Acanthopleura granulata (courtesy of Ling Li). (H) The compound simple eye of the polychaete
worm Spirobranchus corniculatus (courtesy of Michael Bok).
are added—i) membrane proliferation to increase
photopigment areal density and thus sensitivity, ii)
screening pigments to limit the direction of illumination, iii) simple apertures and a small extended
retina to provide rudimentary spatial vision, and ultimately iv) high-quality optics and a multitude of
photoreceptors to reach the upper limits of spatial
resolution. In this view, increasingly high-
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performance eyes often accompany evolution of
more complex body plans and lifestyles. In fact,
even the simplest creatures, as simple as singlecelled dinoflagellates, may incorporate imaging
optics and an extended retina into their one-celled
body plan (Fig. 2). Although the function of such an
excellent miniature ‘‘eye’’ is unknown, it certainly
could be involved in directing more complex behavior than would be possible with the simple shielded
eyespots of other unicellular algae (Colley and
Nilsson 2016).
But of course, evolution does not move along a
track, and there are many examples of eye degeneration as animal lineages are released from selection for
robust vision, such as can occur when taxa become
sessile, invade the deep sea, or become troglodytic.
These animals may still have visual organs, but they
are generally less complex than the eyes of their ancestors. Similarly, whereas the types of photoreceptor
cells and organs at the left margins of the figure are
suitable for non-visual tasks and may remain along
with the visual organs as the latter evolve (and continue to serve the types of non-visual functions mentioned earlier such as circadian entrainment or
photoperiodism), there is no reason why the photoreceptors of high-quality eyes, or at least their mechanisms, may not be scavenged to complement simpler
structures or organs. The best evidence to suggest this
sort of evolutionary trajectory is the presence of many
retinal visual pigments and mechanisms of phototransduction in places far from the retina, for instance in the distal reaches of the nervous system
or in dermal layers (Kingston and Cronin 2016).
Unanswered questions
We convened this symposium to highlight some important and still unanswered questions in the realm
of photoreception without vision. What sort of diversity exists among these receptors (Fig. 2)? Where
are they found in bodies of organisms? How did they
evolve; what were their ancestors; and what have they
produced as their descendants? What are their major
functions, and how do they create the signals required to execute these functions? Do these functions
overlap with those of visual photoreceptors, and if
so, why do both types of photoreceptors persist in
animals? For that matter, why are so many different
types of opsins—often including both visual and
non-visual types—present in a single organism?
And why do some organisms use cryptochromes
when others seem to use opsins for the same functions (as in circadian timing)? Is all this diversity just
evolutionary experimentation and noise, or are there
T. W. Cronin and S. Johnsen
actual selective advantages to having so many fundamentally different kinds of photoreceptors? When
visual opsins occur in both retinal and extraocular
photoreceptors, are they derived from retinal ancestors (or at least their genes), or do both types of
receptors share a non-visual origin?
These questions and many others are encouraged
by the astonishingly diverse discoveries over many
decades that seem to appear whenever photoreceptors that are not devoted to vision are studied. The
papers that follow offer clues to answering some of
these, and we hope that the symposium stands as a
timely milepost in the journey to understanding how
and why animals devote such evolutionary ingenuity
to getting and using information from light.
Funding
The symposium ‘‘Extracellular, Non-visual, and Simple
Photoreceptors’’ was funded by generous support from
the Society for Integrative and Comparative Biology,
primarily from the Division of Neurobiology. TWC is
supported by funding from the Air Force Office of
Scientific Research (FA9550-12-1-0321).
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