Research status and prospects of intrinsically photosensitive retinal ganglion cells / 国际眼科杂志(Guoji Yanke Zazhi)

A brand-new class of photoreceptors has been identified in the past 20a: intrinsically photosensitive retinal ganglion cells(ipRGC). With melanopsin as its photopigment, ipRGCs transmit light signals to non-imaging brain regions like the suprachiasmatic nucleus(SCN)and the olivary pretectal nucleus(OPN)to regulate circadian photoentrainment and pupillary light reflex; a small portion of the signals are projected to brain imaging regions like the dorsal lateral geniculate nucleus(dLGN)and superior colliculus(SC), to participate in imaging vision. There are six different ipRGC subtypes(M1～M6), each with its own morphological and physiological characteristics. In addition to receiving signaling inputs from the rods and cones, ipRGCs also regulate retinal signals through chemical and electrical synapses and play important roles in visual signaling and visual development. It has been discovered that ipRGCs are implicated in several systemic and ocular illnesses. Overall, various aspects of ipRGC are reviewed including the discovery, general physiological properties, signaling, and the relationship with disease in this work.

The visual basis of the biological clock "sees" the light:intrinsically photosensitive retinal ganglion cells / 中华实验眼科杂志

Mammalian eyes mediate both image-forming and non-image-forming visual functions. Non-image-forming vision provides a measure of the ambient light for the purposes of synchronization of circadian clocks to light/dark cycles and regulation of pupil size,pineal melatonin production and other functions. Traditionally,people used to believe that the classical photoreceptors (rods and cones) regulate both image-forming and non-image-forming visual pathways. However,a small subset of retinal ganglion cells called intrinsically photosensitive RGCs ( ipRGCs) has been identified to be a third type of mammalian photoreceptor and determined to be photosensitive, recently. The discovery of ipRGCs has allowed for rapid progress in the past decade toward understanding the non-image-forming visual system,especially about how the circadian clock complete the synchronization with the light/dark cycle. The anatomical and developmental characteristics of ipRGCs, as well as its biological functions and regulation were reviewed in this paper.

Morphology of intrinsically photosensitive retinal ganglion cells: distinct photoreceptors from rod/cone photoreceptors / 中华实验眼科杂志

Objective This study was to observe the morphology of live intrinsically photosensitive retinal ganglion cells (ipRGCs) at cellular level,and to explore their three-dimensional structure and responses to light in curved retina and the relationship with rod/cone photoreceptors.Methods ipRGCs were identified according to the enhanced green fluorescent potein (EGFP) markers.Two hundred and sixty-three ipRGCs were videoed in mouse whole-mounted retina after strengthening with Lucifer Yellow from patch clamp electrodes.The dendrites and cell bodies were analyzed according to their sublayer-specific localization in inner plexiform layer and ganglion cell layer of curved retina.The relationship with rod/cone system was reconstructed and their functions were speculated.The animal feeding and use was in accordance with the standards set by the ARVO,and the experiment was approved by the Ethic Committee for Experimental Animal of Hubei University of Science and Technology.Results The ipRGCs had strictly sublayer-specific localization in three sublayers of retinal inner plexiform layer.Each sublayer occupies full retina and form photosensitive surface,without any intermediate photosensitive dentric distribution between sublayers.Each ipRGC had randomly dentric distributions among the three sublayer curves,without the specific ON/OFF stratification.The photosensitive sublayers had absolutely perpendicular assignment related to cone/rod photoreceptors.The expression of melanopsin and spike-producing Ca2+/Na+ channels were randomly distributed in M1,M2 and M3 cells.M4 and M5 cells shared the characteristic properties of conventional ganglion cells.Conclusions In contrast to the rod/cone photoreceptors,ipRGCs form multiple-sublayer photosensitive curved surface,which are perpendicular to rod/cone photoreceptors,their photosensitive melanopsin and intrinsic spike-producing channels randomly occupy these specific sublayers,which suggest their distinct functions from rod/cone photoreceptors.

Current researches on the circadian rhythm of patients with glaucoma / 中华实验眼科杂志

Like other mammals,human has obvious circadian rhythm,and light is recognized as the principal circadian synchronizer.Rod/cone photoreceptors of the outer retina and the melanopsin-containing retinal ganglion cells(mcRGCs) of the inner retina mediate non-image forming visual responses including entrainment of the circadian clock to the ambient light,the pupillary light reflex (PLR),and light modulation of activity by means of a set of mcRGCs projecting to the suprachiasmatic nucleus (SCN)through retinohypothalamic tract (RHT).Glaucoma is a group of diseases which cause degenerative changes and loss of RGCs including mcRGCs,so the circadian rhythm of patients with glaucoma will be interrupted.The progress in the study on the effect of glaucoma and experimental hypertension on circadian rhythm was reviewed.

The expression of melanopsin and clock genes in Xenopus laevis melanophores and their modulation by melatonin

Vertebrates have a central clock and also several peripheral clocks. Light responses might result from the integration of light signals by these clocks. The dermal melanophores of Xenopus laevis have a photoreceptor molecule denominated melanopsin (OPN4x). The mechanisms of the circadian clock involve positive and negative feedback. We hypothesize that these dermal melanophores also present peripheral clock characteristics. Using quantitative PCR, we analyzed the pattern of temporal expression of Opn4x and the clock genes Per1, Per2, Bmal1, and Clock in these cells, subjected to a 14-h light:10-h dark (14L:10D) regime or constant darkness (DD). Also, in view of the physiological role of melatonin in the dermal melanophores of X. laevis, we determined whether melatonin modulates the expression of these clock genes. These genes show a time-dependent expression pattern when these cells are exposed to 14L:10D, which differs from the pattern observed under DD. Cells kept in DD for 5 days exhibited overall increased mRNA expression for Opn4x and Clock, and a lower expression for Per1, Per2, and Bmal1. When the cells were kept in DD for 5 days and treated with melatonin for 1 h, 24 h before extraction, the mRNA levels tended to decrease for Opn4x and Clock, did not change for Bmal1, and increased for Per1 and Per2 at different Zeitgeber times (ZT). Although these data are limited to one-day data collection, and therefore preliminary, we suggest that the dermal melanophores of X. laevis might have some characteristics of a peripheral clock, and that melatonin modulates, to a certain extent, melanopsin and clock gene expression.