Alterations of Choroidal Blood Flow Regulation in Young Healthy Subjects with Complement Factor H Polymorphism

A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.     

Effect of histamine and cimetidine on retinal and choroidal blood flow in humans

Intravenous administration of histamine causes an increase in choroidal blood flow and retinal vessel diameter in healthy subjects. The mechanism underlying this effect remains to be elucidated. In the present study, we hypothesized that H2 receptor blockade alters hemodynamic effects of histamine in the choroid and retina. Eighteen healthy male nonsmoking volunteers were included in this randomized, double-masked, placebo-controlled two-way crossover study. Histamine (0.32 microg.kg(-1).min(-1) over 30 min) was infused intravenously in the absence (NaCl as placebo) or presence of the H2 blocker cimetidine (2.3 mg/min over 50 min). Ocular hemodynamic parameters, blood pressure, and intraocular pressure were measured before drug administration, after infusion of cimetidine or placebo, and after coinfusion of histamine. Subfoveal choroidal blood flow and fundus pulsation amplitude were measured with laser-Doppler flowmetry and laser interferometry, respectively. Retinal arterial and venous diameters were measured with a retinal vessel analyzer. Retinal blood velocity was assessed with bidirectional laser-Doppler velocimetry. Histamine increased subfoveal choroidal blood flow (+14 +/- 15%, P < 0.001), fundus pulsation amplitude (+11 +/- 5%, P < 0.001), retinal venous diameter (+3.0 +/- 3.6%, P = 0.002), and retinal arterial diameter (+2.8 +/- 4.2%, P < 0.01) but did not change retinal blood velocity. The H2 antagonist cimetidine had no significant effect on ocular hemodynamic parameters. In addition, cimetidine did not modify effects of histamine on choroidal blood flow, fundus pulsation amplitude, retinal venous diameter, and retinal arterial diameter compared with placebo. The present data confirm that histamine increases choroidal blood flow and retinal vessel diameters in healthy subjects. This ocular vasodilator effect of histamine is, however, not altered by administration of an H2 blocker. Whether the increase in blood flow is mediated via H1 receptors or other hitherto unidentified mechanisms remains to be elucidated.     

Major role for neuronal NO synthase in curtailing choroidal blood flow autoregulation in newborn pig.

We examined whether nitric oxide (NO) generated from neuronal NO synthase (nNOS) contributes to the reduced ability of the newborn to autoregulate retinal blood flow (RBF) and choroidal blood flow (ChBF) during acute rises in perfusion pressure. In newborn pigs (1-2 days old), RBF (measured by microsphere) is autoregulated over a narrow range of perfusion pressure, whereas ChBF is not autoregulated. N(G)-nitro-L-arginine methyl ester (L-NAME) or specific nNOS inhibitors 7-nitroindazole, 3-bromo-7-nitroindazole, and 1-(2-trifluoromethyl-phenyl)imidazole as well as ganglionic blocker hexamethonium, unveiled a ChBF autoregulation as observed in juvenile (4- to 6-wk old) animals, whereas autoregulation of RBF in the newborn was only enhanced by L-NAME. All NOS inhibitors and hexamethonium prevented the hypertension-induced increase in NO mediator cGMP in the choroid. nNOS mRNA expression and activity were three- to fourfold higher in the choroid of newborn pigs than in tissues of juvenile pigs. It is concluded that increased production of NO from nNOS curtails ChBF autoregulation in the newborn and suggests a role for the autonomic nervous system in this important hemodynamic function, whereas, for RBF autoregulation, endothelial NOS seems to exert a more important contribution in limiting autoregulation.     

Nitric oxide regulates retinal vascular tone in humans

The purpose of the present study was to investigate the contribution of basal nitric oxide (NO) on retinal vascular tone in humans. In addition, we set out to elucidate the role of NO in flicker-induced retinal vasodilation in humans. Twelve healthy young subjects were studied in a three-way crossover design. Subjects received an intravenous infusion of either placebo or NG-monomethyl-L-arginine (L-NMMA; 3 or 6 mg/kg over 5 min), an inhibitor of NO synthase. Thereafter, diffuse luminance flicker was consecutively performed for 16, 32, and 64 s at a frequency of 8 Hz. The effect of L-NMMA on retinal arterial and venous diameter was assessed under resting conditions and during the hyperemic flicker response. Retinal vessel diameter was measured with a Zeiss retinal vessel analyzer. L-NMMA significantly reduced arterial diameter (3 mg/kg: -2%; 6 mg/kg: -4%, P < 0.001) and venous diameter (3 mg/kg: -5%; 6 mg/kg: -8%, P < 0.001). After placebo infusion, flicker induced a significant increase in retinal vessel diameter (P < 0.001). At a flicker duration of 64 s, arterial diameter increased by 4% and venous diameter increased by 3%. L-NMMA did not abolish these hyperemic responses but blunted venous vasodilation (P = 0.017) and arterial vasodilation (P = 0.02) in response to flicker stimulation. Our data indicate that NO contributes to basal retinal vascular tone in humans. In addition, NO appears to play a role in flicker-induced vasodilation of the human retinal vasculature.     

Effects of dopamine on human retinal vessel diameter and its modulation during flicker stimulation

We performed a randomized, subject-blinded, placebo and time-controlled, two-way crossover study in 12 healthy male subjects. Placebo or dopamine was administered on two separate study days. After saline infusion, dopamine hydrochloride was infused in three consecutive doses (5, 10, and 15 microg x kg(-1) x min(-1)). Plasma levels of dopamine were determined at each perfusion step. Arterial and venous retinal vessel diameters were measured with the use of a Zeiss retinal vessel analyzer. Diffuse luminance flicker stimuli of 8 Hz were applied for 60 s. Blood pressure and pulse rate were monitored continuously. Flicker stimulation (8 Hz) increased retinal vessel diameters under basal conditions. The response to 8-Hz flicker light was significantly reduced by dopamine administration. In addition, dopamine slightly but significantly increased retinal vessel diameters. Dopamine hydrochloride significantly increased systolic but not diastolic or mean arterial pressure. The present study indicates that dopamine has a distinct effect on retinal vessel diameters also attenuating the flicker-induced response reactivity of retinal vessels. This implies a role of dopamine in retinal blood flow hemodynamics.     

Free fatty acids/triglycerides increase ocular and subcutaneous blood flow

Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU. kg(-1). min(-1)) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 +/- 3% (P < 0.001) and in retinal blood flow by 60 +/- 23% (P = 0.0125). PSV increased by 27 +/- 8% (P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 +/- 38% (P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 +/- 5% (P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome.     

Light induces accumulation of isocitrate lyase mRNA in a carotenoid-deficient mutant of Chlamydomonas reinhardtii

A cDNA with sequence similarity to isocitrate lyase (ICL) genes was isolated from the unicellular eukaryotic green alga Chlamydomonas reinhardtii as a light-induced mRNA in the carotenoid biosynthetic mutant strain FN68. The 416 amino acid open reading frame shows significant sequence similarity to isocitrate lyases of bacteria (70%), molds (48%), yeasts (45%), and plants (47%).Expression of the Chlamydomonas ICL gene was tested in the mutant strain FN68, which when grown in the dark fails to accumulate carotenoids and is deficient in chlorophyll, and in CC400G, a strain that accumulates wild-type levels of carotenoids and chlorophyll. In vegetative CC400G cells, ICL mRNA accumulated to a high level in the dark and declined to a barely detectable level within 30 min of exposure to light. This response was more sensitive to white (tungsten filament) or red light than green or blue light, excluding cryptochrome and rhodopsin as the photoreceptor. These results are consistent with excitation by chlorophyll and/or a phytochrome-related photoreceptor. In vegetative FN68 cells, ICL mRNA abundance was very low in the dark, but increased dramatically in response to light. At intensities above threshold, excitation by far-red or red light-induced ICL mRNA accumulation to the highest levels. The threshold of the response was lowest for far-red and blue light. These results are consistent with excitation of a photochromic far-red-responsive pigment.     

Distribution of melatonin MT1 receptor immunoreactivity in human retina.

Melatonin is synthesized in the pineal gland and retina during the night. Retinal melatonin is believed to be involved in local cellular modulation and in regulation of light-induced entrainment of circadian rhythms. The present study provides the first immunohistochemical evidence for the localization of melatonin 1a-receptor (MT1) in human retina of aged subjects. Ganglion, amacrine, and photoreceptor cells expressed MT1. In addition, MT1 immunoreactivity was localized to cell processes in the inner plexiform layer and to central vessels of the retina, as well as to retinal vessels but not to ciliary or choroidal vessels. These results support a variety of cellular and vascular effects of melatonin in the human retina. Preliminary evidence from patients with Alzheimer's disease (AD) revealed increased MT1 immunoreactivity in ganglion and amacrine cells, as well as in vessels. In AD cases photoreceptor cells were degenerated and showed low MT1 expression.     

糖尿病性视网膜病变术后CRT、SFCT、mALB、MBG、HbA1c水平的变化及相关性

本研究通过观察糖尿病性视网膜病变术后患者黄斑中心凹视网膜厚度,脉络膜厚度,尿微量白蛋白、血糖、糖化血红蛋白的水平,试图了解其差异及相关性。我们选取2016年1月至2017年12月于我院就诊的糖尿病性视网膜病变患者200例,根据其有无视网膜病变、有无肾病、术后有无黄斑水肿分为合并组和未合并组,同时选取100例正常成年人作为对照。观察糖尿病患者和对照组、未合并和合并并发症糖尿病患者的黄斑中心凹视网膜厚度(central retinal thickness, CRT),凹下脉络膜厚度(subfoveal choroidal thickness,SFCT),尿微量白蛋白(microAlbunminuria, mALB)、平均血糖(mean blood glucose, MBG)和糖化血红蛋白(glycated haemoglobin, HbA1c)水平,进一步分析了糖尿病黄斑水肿患者的尿微量白蛋白水平与黄斑中心凹视网膜厚度、脉络膜厚度、血糖、糖化血红蛋白的相关性。研究结果表明,糖尿病组患者的CRT水平较对照组低,SFCT、mALB、MBG和HbA1c水平高于对照组;合并视网膜病变、合并肾病和合并黄斑水肿组患者的CRT水平较未合并组低,SFCT、mALB、MBG和HbA1c水平均高于未合并组;黄斑水肿患者的m ALB水平与CRT水平负相关,与SFCT、MBG和HbA1c水平正相关。本研究得出结论:糖尿病性视网膜病变术后患者黄斑中心凹视网膜厚度(CRT)较薄,脉络膜厚度(SFCT)变厚,且与尿微量白蛋白密切相关。     

Role of fractalkine/CX3CR1 interaction in light-induced photoreceptor degeneration through regulating retinal microglial activation and migration

Background

Excessive exposure to light enhances the progression and severity of some human retinal degenerative diseases. While retinal microglia are likely to be important in neuron damage associated with these diseases, the relationship between photoreceptor damage and microglial activation remains poorly understood. Some recent studies have indicated that the chemokine fractalkine is involved in the pathogenesis of many neurodegenerative diseases. The present study was performed to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degeneration.

Methodology/Principal Findings

Both in vivo and in vitro experiments were involved in the research. In vivo, Sprague–Dawley rats were exposed to blue light for 24 hours. In vitro, the co-culture of primary retinal microglia and a photoreceptor cell line (661W cell) was exposed to blue light for five hours. Some cultures were pretreated by the addition of anti-CX3CR1 neutralizing antibody or recombinant fractalkine. Expression of fractalkine/CX3CR1 and inflammatory cytokines was detected by immunofluorescence, real-time PCR, Western immunoblot analysis, and ELISA assay. TUNEL method was used to detect cell apoptosis. In addition, chemotaxis assay was performed to evaluate the impact of soluble fractalkine on microglial migration. Our results showed that the expression of fractalkine that was significantly upregulated after exposure to light, located mainly at the photoreceptors. The extent of photoreceptor degeneration and microglial migration paralleled the increased level of fractalkine/CX3CR1. Compared with the control, the expression of inflammatory cytokines was significantly downregulated in the anti-CX3CR1 neutralizing antibody-treated group, and the number of photoreceptors was also well preserved. The addition of recombinant full-length fractalkine or soluble fractalkine resulted in fewer TUNEL-positive photoreceptors and an increased number of migratory microglia respectively.

Conclusions/Significance

These findings demonstrate that fractalkine/CX3CR1 interaction may play an important role in the photoreceptor-microglia cross-talk in light-induced photoreceptor degeneration.     

Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia

Oxygen tension (PO2) was measured with microelectrodes within the retina of anesthetized cats during normoxia and hypoxemia (i.e., systemic hypoxia), and photoreceptor oxygen consumption was determined by fitting PO2 measurements to a model of steady-state oxygen diffusion and consumption. Choroidal PO2 fell linearly during hypoxemia, about 0.64 mmHg/mmHg decrease in arterial PO2 (PaO2). The choroidal circulation provided approximately 91% of the photoreceptors' oxygen supply under dark-adapted conditions during both normoxia and hypoxemia. In light adaptation the choroid supplied all of the oxygen during normoxia, but at PaO2's less than 60 mmHg the retinal circulation supplied approximately 10% of the oxygen. In the dark-adapted retina the decrease in choroidal PO2 caused a large decrease in photoreceptor oxygen consumption, from approximately 5.1 ml O2/100 g.min during normoxia to 2.6 ml O2/100 g.min at a PaO2 of 50 mmHg. When the retina was adapted to a rod saturating background, normoxic oxygen consumption was approximately 33% of the dark-adapted value, and hypoxemia caused almost no change in oxygen consumption. This difference in metabolic effects of hypoxemia in light and dark explains why the standing potential of the eye and retinal extracellular potassium concentration were previously found to be more affected by hypoxemia in darkness. Frequency histograms of intraretinal PO2 were used to characterize the oxygenation of the vascularized inner half of the retina, where the oxygen distribution is heterogeneous and simple diffusion models cannot be used. Inner retinal PO2 during normoxia was relatively low: 18 +/- 12 mmHg (mean and SD; n = 8,328 values from 36 profiles) in dark adaptation, and significantly lower, 13 +/- 6 mmHg (n = 4,349 values from 19 profiles) in light adaptation. Even in the dark-adapted retina, 30% of the values were less than 10 mmHg. The mean PO2 in the inner (i.e., proximal) half of the retina was well regulated during hypoxemia. In dark adaptation it was significantly reduced only at PaO2's less than 45 mmHg, and it was reduced less at these PaO2's in light adaptation.     

Negative phototropic response of rhizoid cells in the fern Adiantum capillus-veneris

In general, phototropic responses in land plants are induced by blue light and mediated by blue light receptor phototropins. In many cryptogam plants including the fern Adiantum capillus-veneris, however, red as well as blue light effectively induces a positive phototropic response in protonemal cells. In A. capillus-veneris, the red light effect on the tropistic response is mediated by phytochrome 3 (phy3), a chimeric photoreceptor of phytochrome and full-length phototropin. Here, we report red and blue light-induced negative phototropism in A. capillus-veneris rhizoid cells. Mutants deficient for phy3 lacked red light-induced negative phototropism, indicating that under red light, phy3 mediates negative phototropism in rhizoid cells, contrasting with its role in regulating positive phototropism in protonemal cells. Mutants for phy3 were also partially deficient in rhizoid blue light-induced negative phototropism, suggesting that phy3, in conjunction with phototropins, redundantly mediates the blue light response.     

Opponent and nonopponent contributions to the zebrafish electroretinogram using heterochromatic flicker photometry

While some lower vertebrates, such as zebrafish, do not appear to possess anatomically separate pathways of processing visual information (such as M-pathways and P-pathways), it is believed that separate processing of the visual stimulus (such as luminance and chromatic processing) is a basic requirement of vertebrate vision. In this study, spectral sensitivity functions were obtained from electroretinogram responses to heterochromatic flicker photometry stimuli at several flicker rates, including a low flicker rate (2 Hz), in an attempt to predominantly stimulate chromatic processes and a high flicker rate (16 Hz), in an attempt to predominantly stimulate luminance processes. In addition, chromatic adaptation was used to isolate and examine the temporal properties of the different cone-type contributions to the electroretinogram response. Spectral sensitivity functions based on responses to heterochromatic stimuli of a low flicker rate appeared to receive both opponent and nonopponent contributions; however, when the stimulus flicker rate was high, spectral sensitivity appeared to be a function of only nonopponent mechanisms. Also, the differences in cone contributions to the spectral sensitivity functions across the different flicker rates appear to be related to the temporal properties of the cone contributions to the electroretinogram response.     

Dynamic Increase in Extracellular ATP Accelerates Photoreceptor Cell Apoptosis via Ligation of P2RX7 in Subretinal Hemorrhage

Photoreceptor degeneration is the most critical cause of visual impairment in age-related macular degeneration (AMD). In neovascular form of AMD, severe photoreceptor loss develops with subretinal hemorrhage due to choroidal neovascularization (CNV), growth of abnormal blood vessels from choroidal circulation. However, the detailed mechanisms of this process remain elusive. Here we demonstrate that neovascular AMD with subretinal hemorrhage accompanies a significant increase in extracellular ATP, and that extracellular ATP initiates neurodegenerative processes through specific ligation of Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7; P2X7 receptor). Increased extracellular ATP levels were found in the vitreous samples of AMD patients with subretinal hemorrhage compared to control vitreous samples. Extravascular blood induced a massive release of ATP and photoreceptor cell apoptosis in co-culture with primary retinal cells. Photoreceptor cell apoptosis accompanied mitochondrial apoptotic pathways, namely activation of caspase-9 and translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, as well as TUNEL-detectable DNA fragmentation. These hallmarks of photoreceptor cell apoptosis were prevented by brilliant blue G (BBG), a selective P2RX7 antagonist, which is an approved adjuvant in ocular surgery. Finally, in a mouse model of subretinal hemorrhage, photoreceptor cells degenerated through BBG-inhibitable apoptosis, suggesting that ligation of P2RX7 by extracellular ATP may accelerate photoreceptor cell apoptosis in AMD with subretinal hemorrhage. Our results indicate a novel mechanism that could involve neuronal cell death not only in AMD but also in hemorrhagic disorders in the CNS and encourage the potential application of BBG as a neuroprotective therapy.     

Developmental expression of GLUT2 in the rat retina

We previously demonstrated that GLUT2, a facilitated-diffusion glucose transporter isoform known to play critical roles in the regulation of systemic blood glucose level, is present at the apical ends of Müller cells in the rat retina. As a means of elucidating the ontogeny and possible role(s) of GLUT2 in the developing retina, this study examined its expression at various stages of retinal development by immunofluorescence staining using GLUT2-specific antibody. Evidence of GLUT2 expression first appeared at embryonic day 14 (E14) as linear staining along the boundary between the inner and outer layers of the optic cup, with this staining pattern being present throughout subsequent embryonic and neonatal stages. After the development of photoreceptor cell inner and outer segments (i.e., photoreceptor layer), GLUT2 immunoreactivity was localized along the boundary between the outer nuclear layer and photoreceptor layer. Localization of GLUT2 expression and the timing of its appearance, which coincided with the formation of choriocapillaries, together suggest that GLUT2 is involved in the anterior transport of glucose supplied by choroidal circulation from the early stages of retinal development.     

Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development

Apoptosis is the mode of photoreceptor cell death in many retinal dystrophies. Exposure of Balb/c mice to excessive levels of light induces photoreceptor apoptosis and represents an animal model for the study of retinal degenerations. Caspases have emerged as central regulators of apoptosis, executing this tightly controlled death pathway in many cells. Previously we have reported that light-induced photoreceptor apoptosis occurs independently of one the key executioners of apoptosis, caspase-3. This present study extends these results reporting on the lack of activation of other caspases in this model including caspases-8, -9, -7, and -1. Furthermore, photoreceptor apoptosis cannot be inhibited with the broad range caspase inhibitor zVAD-fmk indicating that light-induced retinal degeneration is caspase-independent. We demonstrate that cytochrome c does not translocate from mitochondria to the cytosol during photoreceptor apoptosis. We also show that during retinal development apoptotic protease activating factor (Apaf-1) protein levels are markedly decreased and this is associated with the inability to activate the mitochondrial caspase cascade in the mature retina. In addition, there is also a significant reduction in expression of caspases-3 and -9 during retinal maturation and these levels do not increase following light exposure. Finally, we show that the calcium-dependent proteases calpains are active during light-induced retinal degeneration and establish that the calcium channel blocker D-cis-diltiazem completely inhibits photoreceptor apoptosis.     

Evidence from studies with acifluorfen for participation of a flavin-cytochrome complex in blue light photoreception for phototropism of oat coleoptiles

The diphenyl ether acifluorfen enhances the blue light-induced absorbance change in Triton X100-solubilized crude membrane preparations from etiolated oat (Avena sativa L. cv. Lodi) coleoptiles. Enhancement of the spectral change is correlated with a change in rate of dark reoxidation of a b-type cytochrome. Similar, although smaller, enhancement was obtained with oxyfluorfen, nitrofen, and bifenox. Light-minus-dark difference spectra in the presence and absence of acifluorfen, and the dithionite-reduced-minus oxidized difference spectrum indicate that acifluorfen is acting specifically at a blue light-sensitive cytochrome-flavin complex. Sodium azide, a flavin inhibitor, decreases the light-induced absorbance change significantly, but does not affect the dark reoxidation of the cytochrome. Hence, it is acting on the light reaction, suggesting that the photoreceptor itself is a flavin. Acifluorfen sensitizes phototropism in dark-grown oat seedlings such that the first positive response occurs with blue light fluences as little as one-third of those required to elicit the same response in seedlings grown in the absence of the herbicide. Both this increase in sensitivity to light and the enhancement of the light-induced cytochrome reduction vary with the applied acifluorfen concentration in a similar manner. The herbicide is without effect either on elongation or on the geotropic response of dark-grown oat seedlings, indicating that acifluorfen is acting specifically close to, or at the photoreceptor end of, the stimulus-response chain. It seems likely that the flavin-cytochrome complex serves to transduce the light signal into curvature in phototropism in oats, with the flavin moiety itself serving as the photoreceptor.