title: Loss of Melanopsin-Expressing Retinal Ganglion Cells in Patients With Diabetic Retinopathy.
abstract: Photo-entrainment of the circadian clock is mediated by melanopsin-expressing retinal ganglion cells (mRGCs) located in the retina. Patients suffering from diabetic retinopathy (DR) show impairment of light regulated circadian activity such as sleep disorders, altered blood pressure, and abnormal melatonin secretion. The aim of this study was to assess the impact of DR on the expression of mRGCs in the human retina.
  
  
  
  The expression of mRGCs and RGCs was determined in eye sections containing retinal tissue from patients with DR (n = 6) and respective age-matched controls (n = 8) using immunohistochemistry by costaining with antibodies against RNA binding protein with multiple splicing (RBPMS), which identified RGCs and melanopsin which identified the mRGCs.
  
  
  
  The expression of RGCs in the retina from patients with severe DR was significantly reduced to a density of 146 ± 76 cells/mm2 compared with controls at 1280 ± 249 cells/mm2. The density of mRGCs was also significantly reduced from 3.12 ± 0.54 cells/mm2 in controls to 0.72 ± 0.18 cells/mm2 in patients with DR, with significant loss of 73.5% and 81.9% in mRGC density in the ganglion cell layer (GCL) and inner nuclear layer (INL), respectively.
  
  
  
  Our findings show that DR affects the expression of mRGCs in the human retina and could explain the abnormal circadian activity observed in patients with DR.
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen.
authors.forename: Elisabeth Anne
authors.initials: EA
authors.lastname: Obara
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen.
authors.forename: Jens
authors.initials: J
authors.lastname: Hannibal
authors.affiliation: Department of Pathology, Rigshospitalet, Eye Pathology Section, University of Copenhagen, Denmark 3Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Heegaard
authors.affiliation: Department of Clinical Biochemistry, Bispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen.
authors.forename: Jan
authors.initials: J
authors.lastname: Fahrenkrug
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D002940:Circadian Rhythm / Q000502:physiology*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D017299:Rod Opsins / Q000096:biosynthesis*; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin