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Dendrite Remodeling and Other Abnormalities in the Retinal Ganglion Cells of Ins2^Akita Diabetic Mice

¹From the Departments of Ophthalmology, ²Public Health Sciences, and ³Cellular and Molecular Physiology, Penn State Retina Research Group, Penn State College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania.

PURPOSE. To determine the extent of retinal ganglion cell loss and morphologic abnormalities in surviving ganglion cells in Ins2^Akita/+ diabetic mice.

METHODS. Mice that expressed cyan fluorescent protein (CFP) or yellow fluorescent protein (YFP) reporter genes under the transcriptional control of the Thy1 promoter were crossed with Ins2^Akita/+ mice. After 3 months of diabetes, the number and morphology of retinal ganglion cells was analyzed by confocal microscopy. The number of CFP-positive retinal ganglion cells was quantified in retinas of Ins2^Akita/+ Thy1-CFP mice. The morphology of surviving cells was examined, and dendritic density was quantified in Ins2^Akita/+ Thy1-YFP mice by using the Sholl analysis.

RESULTS. Thy1-CFP expression was limited to retinal ganglion cell bodies. There was a 16.4% reduction in the density of CFP-positive ganglion cells in the peripheral retina of Ins2^Akita/+ mice compared with wild-type control retinas (P < 0.017), but no significant change in the central retina. Thy1-YFP expression occurred throughout the entire structure of a smaller number of cells, including their soma, axons, and dendrites. Six different morphologic clusters of cells were identified in the mouse retinas. The structure of dendrites of ON-type retinal ganglion cells was affected by diabetes, having 32.4% more dendritic terminals (P < 0.05), 18.6% increase in total dendrite length (P < 0.05), and 15.3% greater dendritic density compared with control retinas, measured by Scholl analysis. Abnormal swelling on somas, axons, and dendrites were noted in all subtypes of ganglion cells including those expressing melanopsin.

CONCLUSIONS. The data show that retinal ganglion cells are lost from the peripheral retina of mice within the first 3 months of diabetes and that the dendrites of surviving large ON-type cells undergo morphologic changes. These abnormalities may explain some of the early anomalies in visual function induced by diabetes.

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