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N. Cuenca, Y. Umino, L. Fernandez-Sanchez, E. Solessio, R. B. Barlow; Hypoglycemia Decreases Synaptic Contacts in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4882. doi: https://doi.org/.
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Metabolic stress from moderate hypoglycemia in mice leads to late-onset loss of retinal and visual function. The purpose of this study is to examine the retina of hypoglycemic mice for possible morphological changes in neurons and circuitry.
We used 11 to 13 month old C57BL/6J mice having a null mutation of the glucagon receptor gene that renders the mice mildly hypoglycemic. We assessed retinal function with the ERG retinal anatomy with single and double immunostaining of cryostat vertical sections with antibodies to gamma-transducin, recoverin, bassoon, kinase-C and calbindin. We imaged the sections with immuno-fluorescence confocal microscopy.
Cone photoreceptor morphology as assessed with antibodies against transducin appears intact. However, antibodies against recoverin reveal a reduction in the population of rod photoreceptors. Kinase-C antibodies show a retraction of dendritic processes of ON-rod bipolar cells with a concominent loss of terminal tips. Calbindin staining shows a retraction of horizontal cell terminals. These changes correlate with an appreciable thinning of the outer plexiform layer. A decrease in bassoon staining in both rod and cone synaptic ribbon terminals points to reduced photoreceptor output to the inner retina. A decreased pairing of pre- and post-synaptic elements visualized with PKC-bassoon immunolabeling confirms the reduction of functional synaptic terminals in the OPL. Horizontal and bipolar cells processes sprout into the ONL in areas close to the optic nerve. These morphological changes in the OPL of hypoglycemic mice correlate with a reduction of the ERG b-wave amplitude.
Synaptic retraction and loss of synaptic contacts between photoreceptor and bipolar and horizontal cells most likely contribute to the loss of retinal function in hypoglycemic mice. This work demonstrates that control of blood glucose levels may be important for preventing loss of vision in retinal diseases related to metabolic stress such as diabetic retinopathy and macular degeneration.
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