Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs)

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  • Mio Akasako Princeton University
  • Meow meow Department of Neurology xxxxxxx University
  • Correspondence:


Intrinsically photosensitive retinal ganglion cell (ipRGC)


M1 - M5

Seung Classificaton

  • m1sw (M1s)
  • m8w (M2s)

Other Classifications

  • ON melanopsin (M2): Cdh3 (Sumbul et al., 2014), 6 (Coombs et al., 2006), C3 (Sun et al., 2002)
  • ON-OFF melanopsin (M3): G12 (Volgyi et al., 2009)

Genetic Marker/Gene Expression


Rods and cones, the two traditional photoreceptors in the retina that allow us to see, were long considered to be the only cells in the mammalian eye that possessed direct photosensitivity. However, a novel type of photoreceptor that differs greatly from these two in both form and function was discovered just over a decade ago. These cells express the photopigment melanopsin (as opposed to rhodopsin of rods and cone opsins of cones). Interestingly, these cells are retinal ganglion cells (RGCs), allowing them to have direct communication with visually sensitive areas of the brain. Intrinsically photosensitive retinal ganglion cells (ipRGCs) encode ambient light levels (irradiance) rather than image-related information, and are best known for their roles in synchronizing circadian rhythms with night and day, and light-mediated pupil constriction. They provide input not only to circadian and pupillary centers, but also to a number of other retinorecipient regions of the brain. Making up <5% of the total number of RGCs in the reitna, ipRGCs are a remarkably rare subpopulation of RGCs. Through immunocytochemistry experiments, the number of ipRGCs per retina have been estimated to be between 500 to 2400 (Berson et al., 2010). Although they were initially thought to be composed of only one type, recent morphological and functional studies indicate that there are in fact several distinct subtypes of ipRGCs, termed M1 through M5.

M1-M5 ipRGC stratification and axonal projections adapted from Schmidt et al., 2011


ipRGCs are characterized by their smaller soma size and large dendritic fields. M1 ipRGCs have been most extensively studied, with sparsely branching dendrites that stratify in the OFF sublamina of the IPL. Among M1s, there are some that have cell bodes in the INL, termed displaced M1s. M2 cells have slightly larger cell bodies than M1s and their dendrites reside in the ON sublamina of the IPL. M3 cells are bistratified, extending their dendrites to both ON and OFF sublaminas. M4 cells are monostratified in the ON sublamina and have the largest somas out of ipRGCs; they are more highly branched and have larger dendritic fields than M1-M3 (Ecker et al., 2010, Estevez et al., 2012). The M5 subtype is highly branched with a small dendritic field, and stratifies in the ON IPL (Ecker et al., 2010, Estevez et al., 2012).

M1 through M3 ipRGCs filled with biocytin. M1s stratify in the OFF sublamina while M2s stratify in the ON sublamina. M3s are bistratified. Adapted from Sand et al., 2012.
Comparison of dendritic field diameter and soma size of M1, M2, and M4 cells. Adapted from Estevez et al., 2012


Morphological and physiological properties of ipRGC subtypes from Schmidt et al., 2011

Axonal Projections

Behavioral Output

ipRGCs play a major role in circadian photoentrainment, pupillary light reflex, light aversion, and mood. Adapted from Lucas 2013


Berson, D.M. (2003). Strange vision: ganglion cells as circadian photoreceptors. Trends Neurosci. 26, 314–320. Pubmed PDF

Berson, D.M., Dunn, F.A., and Takao, M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 1070–1073.

Ecker, J.L., Dumitrescu, O.N., Wong, K.Y., Alam, N.M., Chen, S.-K., LeGates, T., Renna, J.M., Prusky, G.T., Berson, D.M., and Hattar, S. (2010). Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron 67, 49-60.

Estevez, M.E., Fogerson, P.M., Ilardi, M.C., Borghuis, B.G., Chan, E., Weng, S., Auferkorte, O.N., Demb, J.B., and Berson, D.M. (2012). Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. J Neurosci 32, 13608–13620.

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Lucas, R.J., Hattar, S., Takao, M., Berson, D.M., Foster, R.G., and Yau, K.W. (2003). Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299, 245–247.

Matynia, A., Parikh, S., Chen, B., Kim, P., McNeill, D.S., Nusinowitz, S., Evans, C., and Gorin, M.B. (2012). Intrinsically photosensitive retinal ganglion cells are the primary but not exclusive circuit for light aversion. Exp. Eye Res. 105, 60–69.

La Morgia, C., Ross-Cisneros, F.N., Hannibal, J., Montagna, P., Sadun, A.A., and Carelli, V. (2011). Melanopsin-expressing retinal ganglion cells: implications for human diseases. Vision Res. 51, 296–302.

Panda, S., Sato, T.K., Castrucci, A.M., Rollag, M.D., DeGrip, W.J., Hogenesch, J.B., Provencio, I., and Kay, S.A. (2002). Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science 298, 2213–2216.

Provencio I, Rodriguez IR. et al. A novel human opsin in the inner retina. J Neurosci. 2000;20(2):600–5.

Schmidt, T.M., and Kofuji, P. (2011). Structure and Function of Bistratified Intrinsically Photosensitive Retinal Ganglion Cells in the Mouse. J Comp Neurol 519, 1492–1504.