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Fred N Ross-Cisneros, Chiara La Morgia, Billy Xiaoyi Pan, Jens Hannibal, Neil Miller, Valerio Carelli, Alfredo A Sadun; Melanopsin Retinal Ganglion Cells are Spared in Wolfram Syndrome. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1236.
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To examine if melanopsin retinal ganglion cells (mRGCs) are spared in Wolfram Syndrome (WS), an autosomal-recessive disease partly characterized by optic atrophy resulting from the loss of RGCs. The pattern of retinal nerve fiber loss in the optic nerves of WS has been shown to be similar to that seen in Leber hereditary optic neuropathy (LHON), a condition in which mRGCs are known to be spared.
Right eyes were obtained at autopsy from a 25-year-old male WS patient and a 24-year-old healthy male control. Eyes were fixed in formalin within 12 hours, dissected at the horizontal meridian at the level of the optic nerve, processed, embedded into paraffin, and serially cut at 5 µm. Every fifth section was immunostained for melanopsin using an indirect immunoperoxidase staining method with an HRP-bound secondary. Diaminobenzadine was used as the chromogen and tissues were counterstained with hematoxylin. The retinal sections were examined for number, location, and morphology of mRGCs.
The control retina showed a normal cellular architecture. The WS retina demonstrated widespread loss of regular RGCs, especially in the papillomacular bundle region. The average number of mRGCs found in 10 sections from the control patient was 6.0 cells per section. The average number of mRGCs in 10 sections from the WS patient was 5.3 cells per section. For both the control and WS patient, mRGCs and their dendritic arbors were distributed throughout the temporal and nasal retina. The mRGCs found in the macula were approximately equal. They were also found slightly more often in the retinal inner nuclear layer (INL) at 52% and 55% respectively. The morphology of these cells appeared similar in both patients and was characterized by densely stained somas and dendrites. Dendritic arbors from mRGCs in the GCL were found to project to both the inner and outer sublamina of the inner plexiform layer (IPL). Cells in the INL were found to project their dendrites to the outermost sublamina of the IPL.
Our assessment of mRGCs in a WS patient compared with a control demonstrates significant loss of regular RGCs but relative sparing of mRGCs. Remarkably, in the WS patient, we found a higher number of mRGCs in the heavily degenerated temporal zone that includes the papillomacular bundle. This finding supports the existence of an anatomical substrate which would allow for both the pupillary reflex and circadian photoentrainment in WS.
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