Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin-ir (0.63-0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin-ir RGCs, which most likely are involved in different functions.
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Jens
http://orcid.org/0000-0001-9416-0125
J
Hannibal
Department of Ophalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Anders Tolstrup
AT
Christiansen
Department of Ophalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Steffen
S
Heegaard
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Jan
J
Fahrenkrug
Department of Ophalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Jens Folke
JF
Kiilgaard
D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000378:metabolism*; D017299:Rod Opsins / Q000096:biosynthesis*; D000099210:Melanopsin
D017299:Rod Opsins; D000099210:Melanopsin
ChAT; Ctbp2; GAD65; PKC; amacrine cells; bipolar cells; calretinin; melanopsin; tyrosine hydroxylase