Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients

Purpose: Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma.Methods: Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital (Copenhagen, Denmark) for detection of RNA binding protein with multiple splicing (RBPMS) and melanopsin by immunohistochemistry. The density of RBPMS-expressing RGCs and mRGCs in each retina was estimated as the total cell count in the total retinal area analyzed (cell counts/mm2).Results: No significant difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts/mm2, with 75% of all retained mRGCs occurring in the inner nuclear layer.Conclusions: This is the first report illustrating histologic evidence for reduced mRGC density in the ganglion cell layer of retinas with severely staged glaucoma compared with age-matched controls. This result proposes evaluation of mRGCs integrity as a basis for assessing the pathophysiologic disease progression of glaucoma.