Intrinsic Photosensitivity Research Articles

Phototransduction and brain circuitry of non-image-forming vision

Perception of light not only results in image vision, but also modulates a number of biological functions that do not involve image formation, such as pupil light reflex and photoentrainment of circadian rhythm. Such non-image-forming vision is primarily mediated by a subset of retinal ganglion cells, termed as intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin thereby exhibiting intrinsic photosensitivity. Since the groundbreaking discovery of ipRGCs approximately two decades ago, ample evidence suggests that ipRGCs project to various subcortical nuclei, and probably participate in a wider range of physiological processes than initially known. This article reviews important laboratory and clinical evidence and recent progress regarding phototransduction of ipRGCs and brain circuitry in non-image vision.

Synergistic effects of persistent free radicals and visible radiation on peroxymonosulfate activation by ferric citrate for the decomposition of organic contaminants

In this work, persistent free radicals (PFRs) of activated carbon fibers (ACFs) were innovatively coupled with Fe(III)–photocatalysts to construct a distinctive catalytic oxidation system, FeCit@ACFs/PMS/visible light. Herein, PFRs acted as an electron sink by donating electrons to ferric citrate (Cit-Fe), thereby accelerating the ligand-to-metal charge transfer (LMCT) processes that govern the rate-determining step of the reaction transforming Cit-FeIII to Cit-FeII. Moreover, visible radiation can serve as another powerful assistor to further enhance the LMCT processes because Cit-Fe exhibits highly intrinsic photosensitivity. The synergistic enhancement effect of PFRs and visible light endowed the constructed FeCit@ACFs catalyst with strong catalytic activity, which could effectively activate peroxymonosulfate (PMS) to generate reactive oxygen species (ROS) for contaminants decomposition. To investigate the ROS generated in this experiment, we adopted a hybrid method that combines electron paramagnetic resonance technology with different radical scavengers, and the results indicated that OH and SO4− were generated and played a major role in the catalytic oxidation process. This work provided a new insight into the positive role of PFRs and presented an up-to-date research domain of PFRs-enhanced catalysis. It also paved an avenue for developing high-efficiency processes for the generation of ROS, which can be subsequently used in environmental catalysis.

Photo-induced structural changes in Ge-Sb-Se films

Amorphous Ge-Sb-Se thin films have been prepared by the radio-frequency (RF) magnetron co-sputtering deposition technique, and their intrinsic photosensitivity and photo-induced structural changes have been investigated. The results show a crossover from photodarkening (PD) to photobleaching (PB) in the films when the film compositions change from Se-deficient to rich. Further Raman analysis on these as-prepared thin films irradiated with a laser of wavelength 655nm in every five minutes provides direct evidence of photo-induced structure rearrangements.

Intrinsic Photosensitivity Enhances Motility of T Lymphocytes.

Sunlight has important biological effects in human skin. Ultraviolet (UV) light striking the epidermis catalyzes the synthesis of Vitamin D and triggers melanin production. Although a causative element in skin cancers, sunlight is also associated with positive health outcomes including reduced incidences of autoimmune diseases and cancers. The mechanisms, however, by which light affects immune function remain unclear. Here we describe direct photon sensing in human and mouse T lymphocytes, a cell-type highly abundant in skin. Blue light irradiation at low doses (<300 mJ cm−2) triggers synthesis of hydrogen peroxide (H2O2) in T cells revealed by the genetically encoded reporter HyPerRed. In turn, H2O2 activates a Src kinase/phospholipase C-γ1 (PLC-γ1) signaling pathway and Ca2+ mobilization. Pharmacologic inhibition or genetic disruption of Lck kinase, PLC-γ1 or the T cell receptor complex inhibits light-evoked Ca2+ transients. Notably, both light and H2O2 enhance T-cell motility in a Lck-dependent manner. Thus, T lymphocytes possess intrinsic photosensitivity and this property may enhance their motility in skin.

Horizontal cells expressing melanopsin x are novel photoreceptors in the avian inner retina

In the vertebrate retina, three types of photoreceptors-visual photoreceptor cones and rods and the intrinsically photosensitive retinal ganglion cells (ipRGCs)-converged through evolution to detect light and regulate image- and nonimage-forming activities such as photic entrainment of circadian rhythms, pupillary light reflexes, etc. ipRGCs express the nonvisual photopigment melanopsin (OPN4), encoded by two genes: the Xenopus (Opn4x) and mammalian (Opn4m) orthologs. In the chicken retina, both OPN4 proteins are found in ipRGCs, and Opn4x is also present in retinal horizontal cells (HCs), which connect with visual photoreceptors. Here we investigate the intrinsic photosensitivity and functioning of HCs from primary cultures of embryonic retinas at day 15 by using calcium fluorescent fluo4 imaging, pharmacological inhibitory treatments, and Opn4x knockdown. Results show that HCs are avian photoreceptors with a retinal-based OPN4X photopigment conferring intrinsic photosensitivity. Light responses in HCs appear to be driven through an ancient type of phototransduction cascade similar to that in rhabdomeric photoreceptors involving a G-protein q, the activation of phospholipase C, calcium mobilization, and the release of the inhibitory neurotransmitter GABA. Based on their intrinsic photosensitivity, HCs may have a key dual function in the retina of vertebrates, potentially regulating nonvisual tasks together with their sister cells, ipRGCs, and with visual photoreceptors, modulating lateral interactions and retinal processing.

Peripheral Sensory Neurons Expressing Melanopsin Respond to Light.

The ability of light to cause pain is paradoxical. The retina detects light but is devoid of nociceptors while the trigeminal sensory ganglia (TG) contain nociceptors but not photoreceptors. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to mediate light-induced pain but recent evidence raises the possibility of an alternative light responsive pathway independent of the retina and optic nerve. Here, we show that melanopsin is expressed in both human and mouse TG neurons. In mice, they represent 3% of small TG neurons that are preferentially localized in the ophthalmic branch of the trigeminal nerve and are likely nociceptive C fibers and high-threshold mechanoreceptor Aδ fibers based on a strong size-function association. These isolated neurons respond to blue light stimuli with a delayed onset and sustained firing, similar to the melanopsin-dependent intrinsic photosensitivity observed in ipRGCs. Mice with severe bilateral optic nerve crush exhibit no light-induced responses including behavioral light aversion until treated with nitroglycerin, an inducer of migraine in people and migraine-like symptoms in mice. With nitroglycerin, these same mice with optic nerve crush exhibit significant light aversion. Furthermore, this retained light aversion remains dependent on melanopsin-expressing neurons. Our results demonstrate a novel light-responsive neural function independent of the optic nerve that may originate in the peripheral nervous system to provide the first direct mechanism for an alternative light detection pathway that influences motivated behavior.

Back Cover: Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro (Chem. Eur. J. 19/2016)

A facile covalent reaction-induced assembly is introduced to construct monodispersed dipeptide-based nanospheres with excellent biocompatibility. Interestingly, such assembled nanospheres can serve as intrinsic photosensitizers to convert O2 to singlet oxygen (1O2) and exhibit red autofluorescence. Thus, photodynamic therapy in vitro can be achieved effectively. This versatile strategy to fabricate potential intrinsic photosensitizers may be extended to other biomolecules containing primary amine groups. More information can be found in the Communication by J. Li et al. on page 6477 ff.

Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro.

Monodispersed diphenylalanine-based nanospheres with excellent biocompatibility are fabricated through a facile covalent reaction-induced assembly. Interestingly, the nanospheres exhibit red autofluorescence. Most importantly, such assembled dipeptide nanospheres can serve as intrinsic photosensitizer to convert O2 to singlet oxygen ((1) O2 ). Thus, photodynamic therapy in vitro can be achieved effectively. The versatile strategy could be extended to other biomolecules containing a primary amine group for the fabrication of potential intrinsic photosensitizers.

Preparation of a finely patterned LaNiO3 film via chemical modification

In this work, a LaNiO3 precursor with ultraviolet photosensitivity was prepared using lanthanum acetate and nickel acetate as the starting materials, acetylacetone (AcAc) as a chemical modifier, and a mixture of ethylene glycol monomethyl ether and ethanol as the solvent. A chelation reaction occurred between AcAc and Ni3+ ions in the precursor, forming Ni chelates that were photosensitive to ultraviolet light. The as-prepared chelate decomposed upon ultraviolet irradiation, and the decomposition products significantly reduced the solubility of the lanthanum nickelate (LNO) gel films in organic solvents. Taking advantage of the intrinsic photosensitivity of the LNO gel films, LNO films with fine structures were prepared and characterized. The results revealed that micrometer-sized LNO patterns could be prepared using this microfabrication technique that was derived from a sol–gel method. Both patterned and non-patterned LNO gel films displayed almost the same electrical performances.

Blue Multifocal Pupillographic Objective Perimetry in Glaucoma.

This study investigated multifocal pupillographic objective perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. The diagnostic potential for glaucoma is compared between stimuli biased toward either cone input to these cells or their melanopsin response. Nineteen glaucoma patients and 24 normal subjects were tested using mfPOP stimulus protocols with either 33-ms yellow or 750-ms blue stimuli. Subjects' color discrimination was assessed using the Farnsworth 100-hue test. Pupillary responses were measured, and mixed-effects regression was used to quantify results. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. The mean reduction in moderate to severe glaucoma pupil responses using blue mfPOP stimuli was larger but more variable than that of the shorter yellow stimuli (blue: -1.32 dB [t(40) = -2.29; P = 0.027]; yellow: -0.93 dB [t(40) = -3.13; P = 0.003]). Color discrimination decreased significantly with age and glaucoma, with type III blue-yellow anomalies dominating. ROC analysis revealed similar diagnostic accuracies (AUC for eyes classified as moderate to severe; blue: 81.7%, yellow: 83.7). Slightly higher sensitivity and specificity were obtained using blue stimuli in mild disease (AUCs blue: 71.1, cf. yellow: 67.7), although this difference was not significant. In moderate to severe glaucoma, diagnostic accuracy of yellow and blue was similar, but blue stimuli showed limited ability to resolve scotomas. Blue mfPOP stimuli, however, may have advantages over yellow in detecting early glaucoma.

Plasmon-mediated generation of reactive oxygen species from near-infrared light excited gold nanocages for photodynamic therapy in vitro.

We have performed fundamental assays of gold nanocages (AuNCs) as intrinsic inorganic photosensitizers mediating generation of reactive oxygen species (ROS) by plasmon-enabled photochemistry under near-infrared (NIR) one/two-photon irradiation. We disclosed that NIR light excited hot electrons transform into either ROS or hyperthermia. Electron spin resonance spectroscopy was applied to demonstrate the production of three main radical species, namely, singlet oxygen ((1)O2), superoxide radical anion (O2(-•)), and hydroxyl radical ((•)OH). The existence of hot electrons from irradiated AuNCs was confirmed by a well-designed photoelectrochemical experiment based on a three-electrode system. It could be speculated that surface plasmons excited in AuNCs first decay into hot electrons, and then the generated hot electrons sensitize oxygen to form ROS through energy and electron transfer modes. We also compared AuNCs' ROS generation efficiency in different surface chemical environments under one/two-photon irradiation and verified that, compared with one-photon irradiation, two-photon irradiation could bring about much more ROS. Furthermore, in vitro, under two-photon irradiation, ROS can trigger mitochondrial depolarization and caspase protein up-regulation to initiate tumor cell apoptosis. Meanwhile, hyperthermia mainly induces tumor cell necrosis. Our findings suggest that plasmon-mediated ROS and hyperthermia can be facilely regulated for optimized anticancer phototherapy.

Laser-induced disaggregation of TiO2 nanofillers for uniform nanocomposites

Exploiting the intrinsic photosensitivity of TiO2 nanoparticles, we demonstrated how ultraviolet (UV) pulsed laser irradiation of acrylate polymer nanocomposite solutions can separate the initial clusters of these colloidal semiconductor nanorods into clearly distinct units. From the irradiated solutions, optically clear nanocomposite films are obtained which exhibit enhanced optical properties with respect to the nanocomposites obtained without previous UV treatment.

Neurobiologic Mechanisms of Sleep and Wakefulness

Neurobiologic Mechanisms of Sleep and Wakefulness

Photopolymer Materials and Processes for Advanced Technologies

Photopolymers broadly comprise monomers, oligomers, polymers, or mixtures of the aforementioned materials that upon exposure to light undergo photochemical reactions that result in deep-seated changes in their structures which substantially modify their chemical and mechanical properties. Photopolymers may possess chromophores that provide for their intrinsic photosensitivity. Alternatively, other photosensitive molecules may be added that directly or indirectly interact with the photopolymer upon exposure to light to produce the desired property changes. Examples of various types of photopolymers will be presented in this article along with examples of their use in representative applications.

Effect of Counterion on the Solid State Photodegradation Behavior of Prazosin Salts

The effect of counterion was evaluated on the photodegradation behavior of six prazosin salts, viz., prazosin hydrochloride anhydrous, prazosin hydrochloride polyhydrate, prazosin tosylate anhydrous, prazosin tosylate monohydrate, prazosin oxalate dihydrate, and prazosin camsylate anhydrous. The salts were subjected to UV-Visible irradiation in a photostability test chamber for 10 days. The samples were analyzed for chemical changes by a specific stability-indicating high-performance liquid chromatography method. pH of the microenvironment was determined in 10%w/v aqueous slurry of the salts. The observed order of photostability was: prazosin hydrochloride anhydrous>prazosin camsylate anhydrous~prazosin-free base>prazosin hydrochloride polyhydrate>prazosin tosylate anhydrous>prazosin oxalate dihydrate~prazosin tosylate monohydrate. Multivariate analysis of the photodegradation behavior suggested predominant contribution of the state of hydration and also intrinsic photosensitivity of the counterion. Overall, hydrated salts showed higher photodegradation compared to their anhydrous counterparts. Within the anhydrous salts, aromatic and carbonyl counterion-containing salts showed higher susceptibility to light. The pH of microenvironment furthermore contributed to photodegradation of prazosin salts, especially for drug counterions with inherent higher pH. The study reveals importance of selection of a suitable drug salt form for photosensitive drugs during preformulation stage of drug development.

Spectral- and time-resolved phosphorescence of photosensitizers and singlet oxygen: From in vitro towards in vivo

Spectral- and time-resolved infrared phosphorescence set-up was adapted for detection from surfaces of solid samples by utilizing fiber optics. Its abilities are demonstrated on the detection of singlet oxygen photosensitization by intrinsic (protoporphyrin IX synthesized from ALA) and extrinsic (TPPS4 and TMPyP) photosensitizers in in vitro layers of cultured 3T3 murine fibroblasts and HeLa cells mimicking in vivo tissues. Complex decays of phosphorescence of the photosensitizers were detected. The data were approximated by multi-exponential decays, however, no straightforward explanation of the individual components was found. Singlet oxygen phosphorescence kinetics were obtained with rise-times corresponding to singlet oxygen lifetimes ranging from 0.7μs to 1.0μs and single-exponential decay times between 5.3μs and 6.5μs for different photosensitizers and cell lines.

ON ganglion cells are intrinsically photosensitive in the tiger salamander retina

Intrinsically photosensitive retinal ganglion cells (ipRGCs) have been well characterized in mammalian systems, both morphologically and electrophysiologically. They show slow, sustained responses to bright light in the absence of photoreceptor-based input, mediated by the photopigment melanopsin. Only one mammalian melanopsin gene is expressed in a small fraction of the retinal ganglion cell population, but there are two genes for melanopsin among nonmammalian vertebrates that are widely expressed in a variety of retinal and extraretinal cell types, along with other photosensitive pigments. The current study provides an electrophysiological study of ipRGCs in the larval tiger salamander (Ambystoma tigrinum), a nonmammalian vertebrate with a well-characterized retina. The results show that the ipRGC population is equivalent to the ON ganglion cell population in the tiger salamander retina. This sheds light on the evolutionary trajectory and functional significance of intrinsic photosensitivity through the vertebrate lineage and also affects our understanding of ON cell activity and development. We have characterized the nature of the intrinsic responses of the ON cell population, compared intrinsic and synaptically based receptive fields, and quantified the spectrum of the intrinsic activity. A wider action spectrum of intrinsic photosensitivity was obtained than would be expected for a single opsin photopigment, suggesting the expression of multiple photopigments in the salamander ipRGC. J. Comp. Neurol., 2012. © 2011 Wiley Periodials, Inc.

Melanopsin-Positive Intrinsically Photosensitive Retinal Ganglion Cells: From Form to Function

Melanopsin imparts an intrinsic photosensitivity to a subclass of retinal ganglion cells (ipRGCs). Generally thought of as irradiance detectors, ipRGCs target numerous brain regions involved in non-image-forming vision. ipRGCs integrate their intrinsic, melanopsin-mediated light information with rod/cone signals relayed via synaptic connections to influence light-dependent behaviors. Early observations indicated diversity among these cells and recently several specific subtypes have been identified. These subtypes differ in morphological and physiological form, controlling separate functions that range from biological rhythm via circadian photoentrainment, to protective behavioral responses including pupil constriction and light avoidance, and even image-forming vision. In this Mini-Symposium review, we will discuss some recent findings that highlight the diversity in both form and function of these recently discovered atypical photoreceptors.

Intrinsically photosensitive ganglion cells of the primate retina express distinct combinations of inhibitory neurotransmitter receptors

Intrinsically-photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and function as irradiance detectors, responsible for crucial non-image forming visual functions. In addition to their intrinsic photosensitivity, ipRGCs are also activated by synaptic inputs originating at the classical photoreceptors, rods and cones. Little is known about inhibition through these retinal pathways, despite ipRGCs receiving massive synaptic inputs from inhibitory amacrine interneurons. We performed a wide anatomical screening for neurotransmitter receptors possibly involved in the inhibitory modulation of ipRGCs in the macaque retina. We investigated both subtypes of primate ipRGCs described so far and report that outer-stratifying (M1) cells possess mainly GlyR α2 and GABAAR α3 subunits, while inner-stratifying (M2) cells are overall subject to less inhibitory modulation. Our results suggest that M1 and M2 ipRGC subtypes are modulated via distinct inhibitory intraretinal circuits.

Expression of Novel Opsins and Intrinsic Light Responses in the Mammalian Retinal Ganglion Cell Line RGC-5. Presence of OPN5 in the Rat Retina

The vertebrate retina is known to contain three classes of photoreceptor cells: cones and rods responsible for vision, and intrinsically photoresponsive retinal ganglion cells (RGCs) involved in diverse non-visual functions such as photic entrainment of daily rhythms and pupillary light responses. In this paper we investigated the potential intrinsic photoresponsiveness of the rat RGC line, RGC-5, by testing for the presence of visual and non-visual opsins and assessing expression of the immediate-early gene protein c-Fos and changes in intracellular Ca2+mobilization in response to brief light pulses. Cultured RGC-5 cells express a number of photopigment mRNAs such as retinal G protein coupled receptor (RGR), encephalopsin/panopsin (Opn3), neuropsin (Opn5) and cone opsin (Opn1mw) but not melanopsin (Opn4) or rhodopsin. Opn5 immunoreactivity was observed in RGC-5 cells and in the inner retina of rat, mainly localized in the ganglion cell layer (GCL). Furthermore, white light pulses of different intensities and durations elicited changes both in intracellular Ca2+ levels and in the induction of c-Fos protein in RGC-5 cell cultures. The results demonstrate that RGC-5 cells expressing diverse putative functional photopigments display intrinsic photosensitivity which accounts for the photic induction of c-Fos protein and changes in intracellular Ca2+ mobilization. The presence of Opn5 in the GCL of the rat retina suggests the existence of a novel type of photoreceptor cell.