Biology subjects

Vemaraju, S.

Publications and source records attributed to Vemaraju, S..

5 recordsLinked to original sources

bioRxiv2024

OPN5 and TRPV4 subserve intrinsic photosensitivity in mouse corneal epithelium

AbstractThe ocular surface protects the eye from pathogens, mechanical impact and harmful radiation. Excessive exposure of corneal epithelial (CE) layers to ultraviolet B (UVB) photons compromises these protective functions and may be associated with inflammation, pain, vision loss and cancer. We investigated the mechanisms that translate corneal epithelial (CE) transduction of UVB photons into intracellular and inflammatory signaling. Optical imaging in dissociated CECs and intact CE sheets showed rapid, UVB-induced increases in intracellular calcium concentration [Ca2+]i that were partially reduced by the TRPV4 antagonist HC067047, removal of extracellular Ca2+ and knockdown of the Trpv4 gene, and obliterated by depletion of internal calcium stores. Knockdown of neuropsin and inhibition of phospholipase C signaling markedly reduced the amplitude of the evoked calcium signal. UVB photons promoted release of cytokines and chemokines that included interleukins, metalloproteinases and thymic stromal lymphopoietin (TSLP). CECs are thus intrinsically photosensitive, utilizing a rhabdomeric-like phototransduction pathway cou0led to cytokine release to alert trigeminal afferents and stromal keratocytes about the presence of harmful irradiation and protect the visual system from snow blindness, injury, vision loss and cancer.

physiology↗

bioRxiv2019

Adaptive thermogenesis in mice requires adipocyte light-sensing via Opsin 3

Almost all life forms can decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are interpreted as images, and the circadian system, where light entrains a physiological clock. Here we describe a local, non-visual light response in mice that employs encephalopsin (OPN3, a 480 nm, blue light responsive opsin) to regulate the function of adipocytes. Germ line null and adipocyte-specific conditional null mice show a deficit in thermogenesis that is phenocopied in mice under blue-light deficient conditions. We show that blue light stimulation of adipocytes activates hormone sensitive lipase, the rate limiting enzyme in the lipolysis pathway, and that this is OPN3-dependent. Opn3 adipocyte conditional null mice also use reduced levels of fat mass when fasted and cold exposed further suggesting a lipolysis deficit. These data suggest the hypothesis that in mice, a local, OPN3-dependent light response in adipocytes is a mechanism for regulation of energy homeostasis.

physiology↗

bioRxiv2019

Light responses of melanopsin-expressing ganglion cells in the foetal mammalian retina

Sensory stimulation plays a critical role in the maturation of sensory organs and systems. For example, when deprived of light before birth, foetal mouse pups in utero exhibit altered ocular vascular development. Normal vascular development depends on light excitation of melanopsin, a non-rod, non-cone photopigment that is expressed in a subset of ganglion cells (mRGCs) in the retina. However, there is no direct evidence that mRGCs in foetal eyes are light-responsive. Very little is known about how light absorption leads to excitation in these foetal neurons. Using mRGC-specific expression of the calcium indicators GCaMP3 and GCaMP6, we report that foetal mouse mRGCs respond to light as early as 4 days before birth. Further, two distinct Gq/11-G protein family antagonists, FR9000359 and YM-254890, abolish these light responses. TTX, a blocker of voltage-activated sodium channels, reversibly represses light responses, and FPL6417 and L-cis-diltiazem, which modify L-type calcium channels, respectively increase and reduce light responses. Electrophysiological patch pipette recordings show that embryonic mRGCs respond to light of intensity as low as 2.9 x 1012 photons/cm2/s. The present findings demonstrate a heretofore unproven but postulated light sensitivity in the retinas of foetal mice and identify the transduction pathways involved. Surprisingly, mRGCs do not function as completely independent photoreceptors but are electrotonically coupled with other mRGCs. Given that melanopsin is expressed in foetal human retinas, these findings support the idea that the eyes of foetal and early preterm infants are likely to exhibit functional photosensitivity.\n\nKey pointsO_LIMelanopsin is a light-excitable photopigment expressed in a subset of ganglion cell neurons (mRGCs) in the retinas of many different species of vertebrates. In mature animals, light activation of mRGCs modulates many visual adaptive functions including pupil constriction, entrainment of circadian rhythms, mood and learning. In neonatal pups at ages prior to the developmental onset of visual signalling from rods and cones, melanopsin cells mediate photoaversive behaviour. In foetal pups, light activation of melanopsin cells accelerates maturation of the ocular vasculature. Here, we describe and physiologically characterize the light responses of melanopsin ganglion cells in the retinas of foetal pups.\nC_LIO_LIMRGCs in embryonic retinas respond to light at least four days prior to birth and exhibit responses to light of intensity as low as 3 x 1012 photons/cm2/s.\nC_LIO_LIPhototransduction mechanisms include melanopsin activation of Gq/11 - G proteins, voltage-activated sodium currents, and voltage-gated L-type calcium currents.\nC_LIO_LIMRGCs are electrotonically coupled to other mRGCs in foetal retinas.\nC_LIO_LIWe propose that melanopsin-expressing ganglion cells are excited by light while in utero and that this excitation relies, for the most part, on phototransduction pathways that have been described in postnatal retinas. Furthermore, we propose that foetal mRGCs have the requisite properties to modulate light-regulated maturation of the ocular vasculature and, perhaps, the development of visual pathways.\nC_LI

neuroscience↗

bioRxiv2019

Fetal stage melanopsin (OPN4) and GNAQ (Gαq) signaling regulates vascular development of the eye

Maturation of sensory systems in mammals is regulated by appropriate sensory stimulation. Developmental refinement of the eye and visual system is regulated by light and visual stimulation. One compelling example is that fetal mouse pups deprived of light exhibit altered vascular development in their eyes. Previous work demonstrated that light activation of the photopigment melanopsin (Opn4), an atypical opsin expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), is crucial to normal vascular development. This suggested the unusual hypothesis that vascular development of the eye was regulated by ipRGC responses in the fetal eye by light that traveled through the body wall of the mother. Here, we test the requirement of OPN4 during fetal stages using genetic approaches. The G-protein GNAQ (Gq) is a candidate mediator of melanopsin signaling. We show that ipRGC-specific deletion of Gnaq phenocopies both hyaloid and retinal vascular development of the Opn4 null mouse. Furthermore, GNAQ gain-of-function in Opn4-expressing cells only during late gestation was sufficient to reverse the consequences for vascular development of either dark rearing or Opn4 loss-of-function. We conclude that melanopsin-dependent signaling in the fetal mouse eye is necessary and sufficient for vascular maturation.

developmental biology↗

bioRxiv2018

An adipocyte light-Opsin 3 pathway regulates the circadian clock and energy balance.

Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, where photoreceptor signals are processed into virtual images, and the circadian system, where light entrains a physiological clock. Here we describe a pathway in mice that employs encephalopsin (OPN3, a 480 nm light responsive opsin) to mediate light responses in murine adipocytes. The adipocyte light-OPN3 pathway regulates neonatal growth in mice and is required for at least three important functions including (1) photoentrainment of a local circadian clock, (2) extracellular matrix deposition, and (3) regulation of mitochondrial content and the proportion of \"brite\" adipocytes. Furthermore, we show that the light-OPN3 pathway is required for normal levels of uncoupling protein 1 (UCP1) in white and brown adipose tissue. Consequently, neonatal Opn3 germ-line and adipocyte-conditional null mice show a reduced ability to maintain their body temperature under cold stress. This was also observed in wild-type mice deprived of blue light. We hypothesize that the adipocyte light-OPN3 pathway provides a dynamically responsive, circadian clock-integrated mechanism for regulating adipocyte function and in turn directing metabolism to thermogenesis rather than anabolism. These data indicate an important role for peripheral light sensing in mammals and may have broad implications for human health given the unnatural lighting conditions in which we live.

physiology↗